Wirkmechanismen von Inhalationsnoxen in Umwelt und Beruf

Zusammenfassung

Im Mittelpunkt dieser Übersicht stehen entzündliche Veränderungen der Atemwegsschleimhaut durch Inhalationsnoxen. Besonders relevant sind Stäube, SO₂, Ozon, Aldehyde und flüchtige organische Verbindungen. Bioorganische Verunreinigungen, vor allem Fragmente von Bakterien und Pilzen, kommen vorwiegend in Innenraumstäuben vor. Sie aktivieren den Toll-like/IL-1-Rezeptor und führen über die Aktivierung des Transkriptionsfaktors NF-κB zur Freisetzung zahlreicher proinflammatorischer Zytokine. Metalle überwiegen in Außenluftstäuben. Sie induzieren die Freisetzung von reaktiven Sauerstoffspezies, die Schäden an Lipiden, Proteinen und DNA der Zelle verursachen. Über Stress-aktivierte-Proteinkinasen werden neben NF-κB proliferationsfördernde Transkriptionsfaktoren aktiviert. Organische Verbindungen, wie polyzyklische aromatische Kohlenwasserstoffe und Nitrosoverbindungen aus Verbrennungsvorgängen, aktivieren zusätzlich über den zytosolischen Arylhydrokarbonrezeptor Gene für Detoxifikationsenzyme. Schwefeldioxid führt zu Säurestress und Ozon zu oxidativem Stress der Zelle, der mit der Freisetzung proinflammatorischer Zytokine über Stress-aktivierte-Proteinkinasen einhergeht. Aldehyde und flüchtige organische Verbindungen aktivieren den Vanilloid-Rezeptor trigeminaler Nervenfasern und induzieren über die Freisetzung von Nervenwachstumsfaktoren eine Schleimhauthyperreagibilität. Die beschriebenen Mechanismen wirken synergistisch und führen zu einer chronischen Entzündungsreaktion der Schleimhaut der oberen Atemwege, die bei den Bürgern westlicher Industrienationen regelhaft nachweisbar ist. Es ist unklar, ob es sich hierbei um eine physiologische Entzündung handelt oder um eine zumindest teilweise vermeidbare Folge chronischer Schadstoffexposition.

Schlüsselwörter

Respiratorische Schleimhaut - Toxikologie - Endotoxine - Metalle - polyzyklische aromatische Kohlenwasserstoffe - Stickstoffmonoxid - reaktive Sauerstoffspezies - Zellmembranrezeptoren - Signaltransduktion - Transkriptionsfaktoren

Literatur

• 1 von-Mutius E, Sherrill D L, Fritzsch C, Martinez F D, Lebowitz M D. Air pollution and upper respiratory symptoms in children from East Germany.  Eur Respir J. 1995;  8 723-728
• 2 Calderon-Garciduenas L, Rodriguez-Alcaraz A, Villarreal-Calderon A, Lyght O, Janszen D, Morgan K T. Nasal epithelium as a sentinel for airborne environmental pollution.  Toxicol Sci. 1998;  46 352-364
• 3 Keles N, Ilicali O C, Deger K. Impact of air pollution on prevalence of rhinitis in Istanbul.  Arch Environ Health. 1999;  54 48-51
• 4 Keles N, Ilicali C. The impact of outdoor pollution on upper respiratory diseases.  Rhinology. 1998;  36 24-27
• 5 Abbey D E, Hwang B L, Burchette R J, Vancuren T, Mills P K. Estimated long-term ambient concentrations of PM10 and development of respiratory symptoms in a nonsmoking population.  Arch Environ Health. 1995;  50 139-152
• 6 Pope C A, Bates D V, Raizenne M E. Health effects of particulate air pollution: time for reassessment?.  Environ Health Pers. 1995;  103 472-780
• 7 Hajat S, Anderson H R, Atkinson R W, Haines A. Effects of air pollution on general practitioner consultations for upper respiratory diseases in London.  Occup Environ Med. 2002;  59 294-299
• 8 Jaakkola J J, Paunio M, Virtanen M, Heinonen O P. Low-level air pollution and upper respiratory infections in children.  Am J Public Health. 1991;  81 1060-1063
• 9 Gordian M E, Ozkaynak H, Xue J, Morris S S, Spengler J D. Particulate air pollution and respiratory disease in Anchorage, Alaska.  Environ Health Perspect. 1996;  104 290-297
• 10 Ostro B D, Eskeland G S, Sanchez J M, Feyzioglu T. Air pollution and health effects: A study of medical visits among children in Santiago, Chile.  Environ Health Perspect. 1999;  107 69-73
• 11 van der Zee S C, Hoek G, Boezen M H, Schouten J P, van Wijnen J H, Brunekreef B. Acute effects of air pollution on respiratory health of 50 - 70 yr old adults.  Eur Respir J. 2000;  15 700-709
• 12 Riechelmann H. Berufliche Verursachung und Bewertung von Mundhöhlen- und Rachentumoren.  Laryngo-Rhino-Otol. 2002;  81 573-579
• 13 Riechelmann H. Umweltmedizin in der HNO-Heilkunde.  Laryngo-Rhino-Otol. 2000;  79 100-127
• 14 Oehlmann J, Markert B. Humantoxikologie. Stuttgart; Wissenschaftliche Verlagsgesellschaft mbH 1997
• 15 Römpp Chemie Lexikon. 9. Auflage ed. Stuttgart, New York; Thieme Verlag 1995
• 16 Medinsky M A, Bond J A. Sites and mechanisms for uptake of gases and vapors in the respiratory tract.  Toxicology. 2001;  160 165-172
• 17 Samet J M. The relationship between acute and chronic health effects of air pollution. In: Bates DV, Brain JD, Driscoll KE, Dungworth DL, Grafström R, Harris CC et al. (eds) Relationships between acute and chronic effects of air pollution. Washington; ILSI Press 2000: 11-21
• 18 Deutsche Forschungsgemeinschaft: Senatskommission zur Prüfung  gesundheitsschädlicher Arbeitsstoffe. MAK- und BAT-Werte-Liste. Weinheim; VCH Verlagsgesellschaft mbH 1996
• 19 Jarabek A M. Inhalation RfC methodology: dosimetric adjustments and dose-response estimation of noncancer toxicity in the upper respiratory tract. In: Miller FJ (ed) Nasal toxicity and dosimetry of inhaled xenobiotics. Washington; Taylor and Francis 1995: 301-325
• 20 Kaliner M A, Shelhamer J H, Borson D B, Patow C A, Nadel J A, Marom Z. Respiratory mucus. In: Kaliner MA, Barnes PJ (eds) The airways, neural control in health and disease. New York; Dekker 1988: 575-593
• 21 Lucas A M, Douglas L C. Principles underlying ciliary activity in the respiratory tract. II. A comparison of nasal clearance in man, monkey and other mammals.  Arch of Otolaryngology. 1934;  20 518-541
• 22 Nadel J A, Widdicombe J H, Peatfield A C. Regulation of airway secretion, ion transport, and water movement. In: Fishman AP (ed) The Respiratory System. Handbook of Physiology. Bethesda CMA; American Physiological Society 1985: 419-445
• 23 Lamblin G, Aubert J P, Perini J M, Klein A, Porchet N, Degand P. et al . Human respiratory mucins.  Eur Respir J. 1992;  5 247-256
• 24 Kim K C, Hisatsune A, Kim D J, Miyata T. Pharmacology of airway goblet cell mucin release.  J Pharmacol Sci. 2003;  92 301-307
• 25 Sharma P, Dudus L, Nielsen P A, Clausen H, Yankaskas J R, Hollingsworth M A. et al . MUC5B and MUC7 are differentially expressed in mucous and serous cells of submucosal glands in human bronchial airways.  Am J Respir Cell Mol Biol. 1998;  19 30-37
• 26 Reid C J, Gould S, Harris A. Developmental expression of mucin genes in the human respiratory tract.  Am J Respir Cell and Molecular Biol. 1997;  17 592-598
• 27 Gray T, Koo J S, Nettesheim P. Regulation of mucous differentiation and mucin gene expression in the tracheobronchial epithelium.  Toxicology. 2001;  160 35-46
• 28 Carraway K L, Ramsauer V P, Haq B, Carothers Carraway C A. Cell signaling through membrane mucins.  Bioessays. 2003;  25 66-71
• 29 Basbaum C, Lemjabbar H, Longphre M, Li D, Gensch E, McNamara N. Control of mucin transcription by diverse injury-induced signaling pathways.  Am J Respir Crit Care Med. 1999;  160 S44-S48
• 30 Basbaum C, Li D, Gensch E, Gallup M, Lemjabbar H. Mechanisms by which gram-positive bacteria and tobacco smoke stimulate mucin induction through the epidermal growth factor receptor (EGFR).  Novartis Found Symp. 2002;  248 171-176
• 31 Rose M C, Piazza F M, Chen Y A, Alimam M Z, Bautista M V, Letwin N. et al . Model systems for investigating mucin gene expression in airway diseases.  J Aerosol Med. 2000;  13 245-261
• 32 Holma B. Influence of buffer capacity and pH-dependant rheological properties of respiratory mucus on health effects due to acid pollution.  Sci Tot Environ. 1985;  41 101-123
• 33 Holma B. Effects of inhaled acids on airway mucus and its consequences for health.  Environ Health Persp. 1989;  79 109-113
• 34 Buhrmester C C. A study of the hydrogen-ion concentration, nitrogen content and viscosity of nasal secretions.  Ann Oto Rhino Laryngol. 1933;  42 1041-1057
• 35 Stierna P, Soederlund K, Hultman E. Chronic maxillary sinusitis. Energy metabolism in sinus mucosa and secretion.  Acta Otolaryngol. 1991;  111 135-143
• 36 van de Donk H, Zuidema J, Merkus F. The influence of the pH and osmotic pressure upon tracheal ciliary beat frequency as determined with a new photo-electric registration device.  Rhinology. 1980;  18 93-104
• 37 Luk C K, Dulfano M J. Effect of pH, viscosity, and ionic strength on ciliary beating frequency of human bronchial explants.  Am Rev Resp Dis Suppl. 1982;  4 244
• 38 Keck T, Leiacker R, Klotz M, Lindemann J, Riechelmann H, Rettinger G. Detection of particles within the nasal airways during respiration.  Eur Arch Otorhinolaryngol. 2000;  257 493-497
• 39 Boland S, Baeza-Squiban A, Fournier T, Houcine O, Gendron M C, Chevrier M. et al . Diesel exhaust particles are taken up by human airway epithelial cells in vitro and alter cytokine production.  Am J Physiol. 1999;  276 604-613
• 40 Kennedy T, Ghio A J, Reed W, Samet J, Zagorski J, Quay J. et al . Copper-dependent inflammation and nuclear factor-κB activation by particulate air pollution.  Am J Respir Cell Mol Biol. 1998;  19 366-378
• 41 Ohkubo K, Baraniuk J N, Hohman R, Merida M, Hersh L B, Kaliner M A. Aminopeptidase activity in human nasal mucosa.  J Allergy Clin Immunol. 1998;  102 741-750
• 42 Grouzmann E, Monod M, Landis B, Wilk S, Brakch N, Nicoucar K. et al . Loss of dipeptidylpeptidase IV activity in chronic rhinosinusitis contributes to the neurogenic inflammation induced by substance P in the nasal mucosa.  Faseb J. 2002;  16 1132-1134
• 43 van der Vliet A, O'Neill C A, Cross C E, Koostra J M, Volz W G, Halliwell B. et al . Determination of low-molecular-mass antioxidant concentrations in human respiratory tract lining fluids.  Am J Physiol. 1999;  276 L289-L296
• 44 Pacht E R, Davis W B. Role of transferrin and ceruloplasmin in antioxidant activity of lung epithelial lining fluid.  J Appl Physiol. 1988;  64 2092-2099
• 45 Blomberg A, Sainsbury C, Rudell B, Frew A J, Holgate S T, Sandstrom T. et al . Nasal cavity lining fluid ascorbic acid concentration increases in healthy human volunteers following short-term exposure to diesel exhaust.  Free Radic Res. 1998;  28 59-67
• 46 Ghio A J, Carter J D, Dailey L A, Devlin R B, Samet J M. Respiratory epithelial cells demonstrate lactoferrin receptors that increase after metal exposure.  Am J Physiol. 1999;  276 L933-L940
• 47 Elsbach P, Weiss J, Levy O. Oxygen-independent antimicrobial systems of phagocytes. In: Gallin JI, Snyderman R (eds) Inflammation basic principles and clinical correlates. Philadelphia, PA; Lippincott Williams & Wilkins 1999: 801-817
• 48 Wang X, Zhang Z, Louboutin J P, Moser C, Weiner D J, Wilson J M. Airway epithelia regulate expression of human β-defensin 2 through Toll-like receptor 2.  Faseb J. 2003;  17 1727-1729
• 49 van Wetering S, Sterk P J, Rabe K F, Hiemstra P S. Defensins: key players or bystanders in infection, injury, and repair in the lung?.  J Allergy Clin Immunol. 1999;  104 1131-1138
• 50 Harder J, Meyer-Hoffert U, Teran L M, Schwichtenberg L, Bartels J, Maune S. et al . Mucoid pseudomonas aeruginosa, TNF-alpha, and IL-1beta, but not IL-6, induce human β-defensin-2 in respiratory epithelia.  Am J Respir Cell Mol Biol. 2000;  22 714-721
• 51 Thornton-Manning J R, Dahl A R. Metabolic capacity of nasal tissue interspecies comparisons of xenobiotic-metabolizing enzymes.  Mutat Res. 1997;  380 43-59
• 52 Blanchard K T, Morris J B. Effects of m-xylene on rat nasal cytochrome P450 mixed function oxidase activities.  Toxicol Lett. 1994;  70 253-259
• 53 Sarkar M A. Drug metabolism in the nasal mucosa.  Pharm Res. 1992;  9 1-9
• 54 Gervasi P G, Longo V, Naldi F, Panattoni G, Ursino F. Xenobiotic-metabolizing enzymes in human respiratory nasal mucosa.  Biochem Pharmacol. 1991;  41 177-184
• 55 Dahl A R, Hadley W M. Nasal cavity enzymes involved in xenobiotic metabolism: effects on the toxicity of inhalants.  Crit Rev Toxicol. 1991;  21 345-372
• 56 Bogdanffy M S. Biotransformation enzymes in the rodent nasal mucosa: the value of a histochemical approach.  Environ Health Perspect. 1990;  85 177-186
• 57 Brittebo E B, Castonguay A, Rafter J J, Kowalski B, Ahlman M, Brandt I. Metabolism of xenobiotics and steroid hormones in the nasal mucosa. In: Barrow C (ed) Toxicology of the nasal passages. Washington, New York, London; Hemisphere Publishing Corporation 1986: 211-234
• 58 Bonvallot V, Baeza-Squiban A, Baulig A, Brulant S, Boland S, Muzeau F. et al . Organic compounds from diesel exhaust particles elicit a proinflammatory response in human airway epithelial cells and induce cytochrome p450 1A1 expression.  Am J Respir Cell Mol Biol. 2001;  25 515-521
• 59 Gronau S, König-Greger D, Rettinger G, Riechelmann H. GSTM1-Genpolymorphismus bei Patienten mit Kopf-Hals-Tumoren.  Laryngo-Rhino-Otol. 2000;  79 341-344
• 60 Gronau S, König-Greger D, Jerg M, Riechelmann H. Gene polymorphisms in detoxification enzymes as susceptibility factor for head and neck cancer?.  Otolaryngol Head Neck Surg. 2003;  128 674-680
• 61 Gronau S, König-Greger D, Jerg M, Riechelmann H. 11Beta-hydroxysteroid dehydrogenase 1 expression in squamous cell carcinomas of the head and neck.  Clin Otolaryngol. 2002;  27 453-457
• 62 Ding X, Kaminsky L S. Human extrahepatic cytochromes P450: function in xenobiotic metabolism and tissue-selective chemical toxicity in the respiratory and gastrointestinal tracts.  Annu Rev Pharmacol Toxicol. 2003;  43 149-173
• 63 Willey J C, Crawford J T, Olson G, Hammersley J E, Jenning C A, Weaver L. et al .Expression measurement of genes related to cancer susceptibility in human bronchial epithelial cells. In: Bates DV, Brain JD, Driscoll KE, Dungworth DL, Grafström R, Harris CC et al. (eds) Relationships between acute and chronic effects of air pollution. Washington; ILSI Press 2000: 79-96
• 64 Wanner A. Allergic mucociliary dysfunction.  Laryngoscope. 1983;  93 68-70
• 65 Scott G, Leopardi S, Parker L, Babiarz L, Seiberg M, Han R. The proteinase-activated receptor-2 mediates phagocytosis in a Rho-dependent manner in human keratinocytes.  J Invest Dermatol. 2003;  121 529-541
• 66 Kato T, Yashiro T, Murata Y, Herbert D C, Oshikawa K, Bando M. et al . Evidence that exogenous substances can be phagocytized by alveolar epithelial cells and transported into blood capillaries.  Cell Tissue Res. 2003;  311 47-51
• 67 Travaglione S, Falzano L, Fabbri A, Stringaro A, Fais S, Fiorentini C. Epithelial cells and expression of the phagocytic marker CD68: scavenging of apoptotic bodies following Rho activation.  Toxicol In Vitro. 2002;  16 405-411
• 68 Godleski J J. Cardiovascular responses to inhaled particles. In: Bates DV, Brain JD, Driscoll KE, Dungworth DL, Grafström R, Harris CC et al. (eds) Relationships between acute and chronic effects of air pollution. Washington; ILSI Press 2000: 142-155
• 69 Pope C A, Burnett R T, Thun M J, Calle E E, Krewski D, Ito K. et al . Lung cancer, cardiopulmonary mortality, and long-term exposure to fine particulate air pollution.  Jama. 2002;  287 1132-1141
• 70 Johnson T, Devli R, Ghio A J, Huang Y C, Costa D L, Engle C. et al .Cardiopulmonary effects of nebulized residual oil fly ash in anesthesized pigs. In: Bates DV, Driscoll KE, Dungworth DL, Fabel H, Grafström R, Harkema JR et al. (eds) Crucial issues in inhalation research - mechanistic, clinical and epidemiologic. Stuttgart; Fraunhofer IRB Verlag 2002: 199-212
• 71 Bohm G M, Saldiva P H, Pasqualucci C A, Massad E, Martins M, Zin W A. et al . Biological effects of air pollution in Sao Paulo and Cubatao.  Environ Res. 1989;  49 208-216
• 72 Calderon-Garciduenas L, Rodriguez-Alcaraz A, Garcia R, Sanchez G, Barragan G, Camacho R. et al . Human nasal mucosal changes after exposure to urban pollution.  Environ Health Perspect. 1994;  102 1074-1080
• 73 Calderon-Garciduenas L, Rodriguez-Alcaraz A, Garcia R, Ramirez L, Barragan G. Nasal inflammatory responses in children exposed to a polluted urban atmosphere.  J Toxicol Environ Health. 1995;  45 427-437
• 74 Calderon-Garciduenas L, Rodriguez-Alcaraz A, Valencia-Salazar G, Mora-Tascareno A, Garcia R, Osnaya N. et al . Nasal biopsies of children exposed to air pollutants.  Toxicol Pathol. 2001;  29 558-564
• 75 Calderon-Garciduenas L, Valencia-Salazar G, Rodriguez-Alcaraz A, Gambling T M, Garcia R, Osnaya N. et al . Ultrastructural nasal pathology in children chronically and sequentially exposed to air pollutants.  Am J Respir Cell Mol Biol. 2001;  24 132-138
• 76 Kreyling W G, Dirscherl P, Ferron G A, Heilmann P, Josten M, Miaskowski U. et al . Health effects of sulfur-related environmental air pollution. III. Nonspecific respiratory defense capacities.  Inhal Toxicol. 1999;  11 391-422
• 77 Lastbom B L, Camner P. Human experimental studies on the effects of inhaled particles.  Scand J Work Environ Health. 2000;  26 43-48
• 78 Mochca-Morales J. Nasal albumin in a population exposed for the first time to urban pollution.  Arch Med Res. 2000;  31 409-414
• 79 Moss O R, Gross E A, James R A, Janszen D B, Ross P W, Roberts K C. et al . Respiratory tract toxicity in rats exposed to Mexico City air.  Res Rep Health Eff Inst. 2001;  100 1-24
• 80 Saldiva P H, King M, Delmonte V L, Macchione M, Parada M A, Daliberto M L. et al . Respiratory alterations due to urban air pollution: an experimental study in rats.  Environ Res. 1992;  57 19-33
• 81 Shusterman D. Toxicology of nasal irritants.  Curr Allergy Asthma Rep. 2003;  3 258-265
• 82 Baeza-Squiban A, Bonvallot V, Boland S, Marano F. Airborne particles evoke an inflammatory response in human airway epithelium. Activation of transcription factors.  Cell Biol Toxicol. 1999;  15 375-380
• 83 Calderon-Garciduenas L, Devlin R B, Miller F J. Respiratory tract pathology and cytokine imbalance in clinically healthy children chronically and sequentially exposed to air pollutants.  Med Hypotheses. 2000;  55 373-378
• 84 Carter J D, Ghio A J, Samet J M, Devlin R B. Cytokine production by human airway epithelial cells after exposure to an air pollution particle is metal-dependent.  Toxicol Appl Pharmacol. 1997;  146 180-188
• 85 Devalia J L, Bayram H, Rusznak C, Calderon M, Sapsford R J, Abdelaziz M A. et al . Mechanisms of pollution-induced airway disease: in vitro studies in the upper and lower airways.  Allergy. 1997;  52 45-51
• 86 Douwes J, Wouters I, Dubbeld H, van Zwieten L, Steerenberg P, Doekes G. et al . Upper airway inflammation assessed by nasal lavage in compost workers: A relation with bio-aerosol exposure.  Am J Ind Med. 2000;  37 459-468
• 87 Fujii T, Hayashi S, Hogg J C, Vincent R, van Eeden S F. Particulate matter induces cytokine expression in human bronchial epithelial cells.  Am J Respir Cell Mol Biol. 2001;  25 265-271
• 88 Hashimoto S, Gon Y, Takeshita I, Matsumoto K, Jibiki I, Takizawa H. et al . Diesel exhaust particles activate p38 MAP kinase to produce interleukin 8 and RANTES by human bronchial epithelial cells and N-acetylcysteine attenuates p38 MAP kinase activation.  Am J Respir Crit Care Med. 2000;  161 280-285
• 89 Hirvonen M R, Ruotsalainen M, Roponen M, Hyvarinen A, Husman T, Kosma V M. et al . Nitric oxide and proinflammatory cytokines in nasal lavage fluid associated with symptoms and exposure to moldy building microbes.  Am J Respir Crit Care Med. 1999;  160 1943-1946
• 90 Jimenez L A, Drost E M, Gilmour P S, Rahman I, Antonicelli F, Ritchie H. et al . PM(10)-exposed macrophages stimulate a proinflammatory response in lung epithelial cells via TNF-alpha.  Am J Physiol Lung Cell Mol Physiol. 2002;  282 L237-L248
• 91 Krishna M T, Chauhan A J, Frew A J, Holgate S T. Toxicological mechanisms underlying oxidant pollutant-induced airway injury.  Rev Environ Health. 1998;  13 59-71
• 92 Long C M, Suh H H, Kobzik L, Catalano P J, Ning Y Y, Koutrakis P. A pilot investigation of the relative toxicity of indoor and outdoor fine particles: in vitro effects of endotoxin and other particulate properties.  Environ Health Perspect. 2001;  109 1019-1026
• 93 Mills P R, Davies R J, Devalia J L. Airway epithelial cells, cytokines, and pollutants.  Am J Respir Crit Care Med. 1999;  160 38-43
• 94 Monn C, Becker S. Cytotoxicity and induction of proinflammatory cytokines from human monocytes exposed to fine (PM2.5) and coarse particles (PM10 - 2.5) in outdoor and indoor air.  Toxicol Appl Pharmacol. 1999;  155 245-252
• 95 Monn C, Naef R, Koller T. Reactions of macrophages exposed to particles < 10 microm.  Environ Res. 2003;  91 35-44
• 96 Ohtoshi T, Takizawa H, Okazaki H, Kawasaki S, Takeuchi N, Ohta K. et al . Diesel exhaust particles stimulate human airway epithelial cells to produce cytokines relevant to airway inflammation in vitro.  J Allergy Clin Immunol. 1998;  101 778-785
• 97 Pei X H, Nakanishi Y, Inoue H, Takayama K, Bai F, Hara N. Polycyclic aromatic hydrocarbons induce IL-8 expression through nuclear factor κB activation in A549 cell line.  Cytokine. 2002;  19 236-241
• 98 Purokivi M K, Hirvonen M R, Randell J T, Roponen M H, Meklin T M, Nevalainen A L. et al . Changes in pro-inflammatory cytokines in association with exposure to moisture-damaged building microbes.  Eur Respir J. 2001;  18 951-958
• 99 Quay J L, Reed W, Samet J, Devlin R B. Air pollution particles induce IL-6 gene expression in human airway epithelial cells via NF-κB activation.  Am J Respir Cell Mol Biol. 1998;  19 98-106
• 100 Saraf A, Larsson L, Larsson B M, Larsson K, Palmberg L. House dust induces IL-6 and IL-8 response in A549 epithelial cells.  Indoor Air. 1999;  9 219-225
• 101 Schierhorn K, Zhang M, Matthias C, Kunkel G. Influence of ozone and nitrogen dioxide on histamine and interleukin formation in a human nasal mucosa culture system.  Am J Respir Cell Mol Biol. 1999;  20 1013-1019
• 102 Shukla A, Timblin C, BeruBe K, Gordon T, McKinney W, Driscoll K. et al . Inhaled particulate matter causes expression of nuclear factor (NF)-κB-related genes and oxidant-dependent NF-κB activation in vitro.  Am J Respir Cell Mol Biol. 2000;  23 182-187
• 103 Steerenberg P A, Fischer P H, van Bree L, van Loveren H. Nasal lavage biomarkers in air pollution epidemiology.  Arch Toxicol Suppl. 1997;  19 207-216
• 104 Takizawa H, Ohtoshi T, Kawasaki S, Abe S, Sugawara I, Nakahara K. et al . Diesel exhaust particles activate human bronchial epithelial cells to express inflammatory mediators in the airways: a review.  Respirology. 2000;  5 197-203
• 105 Tao F, Kobzik L. Lung macrophage-epithelial cell interactions amplify particle-mediated cytokine release.  Am J Respir Cell Mol Biol. 2002;  26 499-505
• 106 van Eeden S F, Tan W C, Suwa T, Mukae H, Terashima T, Fujii T. et al . Cytokines involved in the systemic inflammatory response induced by exposure to particulate matter air pollutants (pm₁₀).  Am J Respir Crit Care Med. 2001;  164 826-830
• 107 Veronesi B, Oortgiesen M, Carter J D, Devlin R B. Particulate matter initiates inflammatory cytokine release by activation of capsaicin and acid receptors in a human bronchial epithelial cell line.  Toxicol Appl Pharmacol. 1999;  154 106-115
• 108 Griego S D, Weston C B, Adams J L, Tal-Singer R, Dillon S B. Role of p38 mitogen-activated protein kinase in rhinovirus-induced cytokine production by bronchial epithelial cells.  J Immunol. 2000;  165 5211-5220
• 109 Altman G B, Altman L C, Luchtel D L, Jabbour A J, Baker C. Release of RANTES from nasal and bronchial epithelial cells.  Cell Biol Toxicol. 1997;  13 205-213
• 110 Bachert C. Die Schleimhaut der oberen Atemwege - Zur Pathophysiologie der Entzündung.  Oto-Rhino-Laryngology. 1995;  Suppl. I 155-220
• 111 Monod J, Wyman J, Changeux J P. On the nature of allosteric transitions: a plausible model.  J Mol Biol. 1965;  12 88-118
• 112 Zhang Y, Reinberg D. Transcription regulation by histone methylation: interplay between different covalent modifications of the core histone tails.  Genes Dev. 2001;  15 2343-2360
• 113 Stamler J S, Lamas S, Fang F C. Nitrosylation. The prototypic redox-based signaling mechanism.  Cell. 2001;  106 675-683
• 114 Park H S, Huh S H, Kim M S, Lee S H, Choi E J. Nitric oxide negatively regulates c-Jun N-terminal kinase/stress-activated protein kinase by means of S-nitrosylation.  Proc Natl Acad Sci USA. 2000;  97 14 382-14 387
• 115 Kim S O, Merchant K, Nudelman R, Beyer W F, Keng T, De Angelo J. et al . OxyR: a molecular code for redox-related signaling.  Cell. 2002;  109 383-396
• 116 Huang S L, Cheng W L, Lee C T, Huang H C, Chan C C. Contribution of endotoxin in macrophage cytokine response to ambient particles in vitro.  J Toxicol Environ Health A. 2002;  65 1261-1272
• 117 Michel O, Nagy A M, Schroeven M, Duchateau J, Neve J, Fondu P. et al . Dose-response relationship to inhaled endotoxin in normal subjects.  Am J Respir Crit Care Med. 1997;  156 1157-1164
• 118 Nightingale J A, Rogers D F, Hart L A, Kharitonov S A, Chung K F, Barnes P J. Effect of inhaled endotoxin on induced sputum in normal, atopic, and atopic asthmatic subjects.  Thorax. 1998;  53 563-571
• 119 Sandstrom T, Bjermer L, Rylander R. Lipopolysaccharide (LPS) inhalation in healthy subjects increases neutrophils, lymphocytes and fibronectin levels in bronchoalveolar lavage fluid.  Eur Respir J. 1992;  5 992-996
• 120 Danuser B, Rebsamen H, Weber C, Krueger H. Lipopolysaccharide-induced nasal cytokine response: a dose-response evaluation.  Eur Arch Otorhinolaryngol. 2000;  257 527-532
• 121 Sigsgaard T, Bonefeld-Jorgensen E C, Kjaergaard S K, Mamas S, Pedersen O F. Cytokine release from the nasal mucosa and whole blood after experimental exposures to organic dusts.  Eur Respir J. 2000;  16 140-145
• 122 Peden D B, Tucker K, Murphy P, Newlin-Clapp L, Boehlecke B, Hazucha M. et al . Eosinophil influx to the nasal airway after local, low-level LPS challenge in humans.  J Allergy Clin Immunol. 1999;  104 388-394
• 123 von Mutius E, Braun-Fahrlander C, Schierl R, Riedler J, Ehlermann S, Maisch S. et al . Exposure to endotoxin or other bacterial components might protect against the development of atopy.  Clin Exp Allergy. 2000;  30 1230-1234
• 124 Myatt T, Milton D. Endotoxins. In: Spengler JD, Samet JM, McCarthy JF (eds) Indoor air quality handbook. New York; McGraw-Hill 2001: 42.1-42.14
• 125 Teeuw K B, Vandenbroucke-Grauls C M, Verhoef J. Airborne gram-negative bacteria and endotoxin in sick building syndrome. A study in Dutch governmental office buildings.  Arch Intern Med. 1994;  154 2339-2345
• 126 Nowak D. Klinisch-experimentelle und epidemiologische Untersuchungen zur Wirkung irritativer Berufs- und Umweltnoxen auf den Atemtrakt. Regensburg; S. Roderer Verlag 1997
• 127 Larsson B M, Larsson K, Malmberg P, Martensson L, Palmberg L. Airway responses in naive subjects to exposure in poultry houses: comparison between cage rearing system and alternative rearing system for laying hens.  Am J Ind Med. 1999;  35 142-149
• 128 Laitinen S, Linnainmaa M, Laitinen J, Kiviranta H, Reiman M, Liesivuori J. Endotoxins and IgG antibodies as indicators of occupational exposure to the microbial contaminants of metal-working fluids.  Int Arch Occup Environ Health. 1999;  72 443-450
• 129 Becker S, Soukup J M, Gilmour M I, Devlin R B. Stimulation of human and rat alveolar macrophages by urban air particulates: effects on oxidant radical generation and cytokine production.  Toxicol Appl Pharmacol. 1996;  141 637-648
• 130 Becker S, Fenton M J, Soukup J M. Involvement of microbial components and toll-like receptors 2 and 4 in cytokine responses to air pollution particles.  Am J Respir Cell Mol Biol. 2002;  27 611-618
• 131 Douwes J, Zuidhof A, Doekes G, van der Zee S C, Wouters I, Boezen M H. et al . (1->3)-beta-D-glucan and endotoxin in house dust and peak flow variability in children.  Am J Respir Crit Care Med. 2000;  162 1348-1354
• 132 Fogelmark B, Goto H, Yuasa K, Marchat B, Rylander R. Acute pulmonary toxicity of inhaled beta-1,3-glucan and endotoxin.  Agents Actions. 1992;  35 50-56
• 133 Gehring U, Douwes J, Doekes G, Koch A, Bischof W, Fahlbusch B. et al . Beta(1->3)-glucan in house dust of German homes: housing characteristics, occupant behavior, and relations with endotoxins, allergens, and molds.  Environ Health Perspect. 2001;  109 139-144
• 134 Imrich A, Ning Y, Kobzik L. Insoluble components of concentrated air particles mediate alveolar macrophage responses in vitro.  Toxicol Appl Pharmacol. 2000;  167 140-150
• 135 Khair O A, Davies R J, Devalia J L. Bacterial-induced release of inflammatory mediators by bronchial epithelial cells.  Eur Respir J. 1996;  9 1913-1922
• 136 Liu A H. Endotoxin exposure in allergy and asthma: reconciling a paradox.  J Allergy Clin Immunol. 2002;  109 379-392
• 137 Long C M, Suh H H, Kobzik L, Catalano P J, Ning Y Y, Koutrakis P. A pilot investigation of the relative toxicity of indoor and outdoor fine particles: in vitro effects of endotoxin and other particulate properties.  Environ Health Perspect. 2001;  109 1019-1026
• 138 Ning Y, Imrich A, Goldsmith C A, Qin G, Kobzik L. Alveolar macrophage cytokine production in response to air particles in vitro: role of endotoxin.  J Toxicol Environ Health A. 2000;  59 165-180
• 139 Park J H, Spiegelman D L, Burge H A, Gold D R, Chew G L, Milton D K. Longitudinal study of dust and airborne endotoxin in the home.  Environ Health Perspect. 2000;  108 1023-1028
• 140 George D, Schwartz D A. The role of endotoxin in acute and chronic grain dust induced airway disease. In: Bates DV, Brain JD, Driscoll KE, Dungworth DL, Grafström R, Harris CC et al. (eds) Relationships between acute and chronic effects of air pollution. Washington; ILSI Press 2000: 169-184
• 141 Parod R J, Brain J D. Immune opsonin-independent phagocytosis by pulmonary macrophages.  The Journal of Immunology. 1986;  136 2041-2047
• 142 Garcia-Garcia E, Rosales C. Signal transduction during Fc receptor-mediated phagocytosis.  J Leukoc Biol. 2002;  72 1092-1108
• 143 Orphanides G, Reinberg D. A unified theory of gene expression.  Cell. 2002;  108 439-451
• 144 Jaspers I, Samet J M, Reed W. Arsenite exposure of cultured airway epithelial cells activates κB-dependent interleukin-8 gene expression in the absence of nuclear factor-κB nuclear translocation.  Journal of Biological Chemistry. 1999;  274 31 025-31 033
• 145 Jaspers I, Samet J, Erzurum S, Reed W. Vanadium-induced κB-dependent transcription depends upon peroxide-induced activation of the p38 mitogen-activated protein kinase.  American Journal of Respiratory Cell and Molecular Biology. 2000;  23 95-102
• 146 Hsu M H, Wang M, Browning D D, Mukaida N, Ye R D. NF-κB activation is required for C5a-induced interleukin-8 gene expression in mononuclear cells.  Blood. 1999;  93 3241-3249
• 147 Pan Z K, Ye R D, Christiansen S C, Jagels M A, Bokoch G M, Zuraw B L. Role of the Rho GTPase in bradykinin-stimulated Nuclear Factor-κB activation and IL-1β gene expression in cultured human epithelial cells.  J Immunol. 1998;  160 3038-3045
• 148 Pei X H, Nakanishi Y, Takayama K, Bai F, Hara N. Benzo[a]pyrene Activates the Human p53 Gene through Induction of Nuclear Factor κB Activity.  Journal of Biological Chemistry. 1999;  274 35 240-35 246
• 149 Kwon O, Lee E, Moon T C, Jung H, Lin C X, Nam K S. et al . Expression of cyclooxygenase-2 and pro-inflammatory cytokines induced by 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153) in human mast cells requires NF-κB activation.  Biol Pharm Bull. 2002;  25 1165-1168
• 150 Desaki M, Takizawa H, Kasama T, Kobayashi K, Morita Y, Yamamoto K. Nuclear factor-kappa b activation in silica-induced interleukin 8 production by human bronchial epithelial cells.  Cytokine. 2000;  12 1257-1260
• 151 Takizawa H, Ohtoshi T, Kawasaki S, Kohyama T, Desaki M, Kasama T. et al . Diesel exhaust particles induce NF-κB activation in human bronchial epithelial cells in vitro: importance in cytokine transcription.  J Immunol. 1999;  162 4705-4711
• 152 Churg A, Wright J L. Airway wall remodeling induced by occupational mineral dusts and air pollutant particles.  Chest. 2002;  122 306S-309S
• 153 Jimenez L A, Thompson J, Brown D A, Rahman I, Antonicelli F, Duffin R. et al . Activation of NF-κB by PM(10) occurs via an iron-mediated mechanism in the absence of IκB degradation.  Toxicol Appl Pharmacol. 2000;  166 101-110
• 154 Peden D B. Pollutants and asthma: role of air toxics.  Environ Health Perspect. 2002;  110 Suppl 4 565-568
• 155 Blackwell T S, Christman J W. The role of Nuclear Factor-κB in cytokine gene regulation.  American Journal of Respiratory Cell and Molecular Biology. 1997;  17 3-9
• 156 Bureau F, Delhalle S, Bonizzi G, Fievez L, Dogne S, Kirschvink N. et al . Mechanisms of persistent NF-κB activity in the bronchi of an animal model of asthma.  J Immunol. 2000;  165 5822-5830
• 157 Mercurio F, Manning A M. Multiple signals converging on NF-κB.  Curr Opin Cell Biol. 1999;  11 226-232
• 158 Hanada T, Yoshimura A. Regulation of cytokine signaling and inflammation.  Cytokine Growth Factor Rev. 2002;  13 413-421
• 159 Christman J W, Sadikot R T, Blackwell T S. The role of nuclear factor-κB in pulmonary diseases.  Chest. 2000;  117 1482-1487
• 160 Quay J L, Reed W, Samet J, Devlin R B. Air pollution particles induce IL-6 gene expression in human airway epithelial cells via NF-κB activation.  Am J Respir Cell Mol Biol. 1998;  19 98-106
• 161 Chimini G, Chavrier P. Function of Rho family proteins in actin dynamics during phagocytosis and engulfment.  Nat Cell Biol. 2000;  2 E191-E196
• 162 Ridley A J. Rho GTPases and cell migration.  J Cell Sci. 2001;  114 2713-2722
• 163 Houle F, Rousseau S, Morrice N, Luc M, Mongrain S, Turner C E. et al . Extracellular signal-regulated kinase mediates phosphorylation of tropomyosin-1 to promote cytoskeleton remodeling in response to oxidative stress: impact on membrane blebbing.  Mol Biol Cell. 2003;  14 1418-1432
• 164 Greenberg S. Biology of phagocytosis. In: Gallin JI, Snyderman R (eds) Inflammation basic principles and clinical correlates. Philadelphia, PA; Lippincott Williams & Wilkins 1999: 681-701
• 165 Stossel T T. Mechanical responses of white blood cells. In: Gallin JI, Snyderman R (eds) Inflammation basic principles and clinical correlates. Philadelphia, PA; Lippincott Williams & Wilkins 1999: 661-679
• 166 DeLeo F R, Allen L A, Apicella M, Nauseef W M. NADPH Oxidase Activation and Assembly During Phagocytosis.  The Journal of Immunology. 1999;  163 6732-6740
• 167 Carreras M C, Riobo N A, Pargament G A, Boveris A, Poderoso J J. Effects of respiratory burst inhibitors on nitric oxide production by human neutrophils.  Free Radic Res. 1997;  26 325-334
• 168 Carreras M C, Pargament G A, Catz S D, Poderoso J J, Boveris A. Kinetics of nitric oxide and hydrogen peroxide production and formation of peroxynitrite during the respiratory burst of human neutrophils.  FEBS Lett. 1994;  341 65-68
• 169 MacMicking J, Xie Q W, Nathan C. Nitric oxide and macrophage function.  Annu Rev Immunol. 1997;  15 323-350
• 170 Bogdan C, Rollinghoff M, Diefenbach A. The role of nitric oxide in innate immunity.  Immunol Rev. 2000;  173 17-26
• 171 Kohen R, Nyska A. Oxidation of biological systems: oxidative stress phenomena, antioxidants, redox reactions, and methods for their quantification.  Toxicol Pathol. 2002;  30 620-650
• 172 Nathan C. Specificity of a third kind: reactive oxygen and nitrogen intermediates in cell signaling.  J Clin Invest. 2003;  111 769-778
• 173 The e ffect. The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group.  N Engl J Med. 1994;  330 1029-1035
• 174 Paolini M, Abdel-Rahman S Z, Cantelli-Forti G, Legator M S. Chemoprevention or antichemoprevention? A salutary warning from the beta-carotene experience.  J Natl Cancer Inst. 2001;  93 1110-1111
• 175 Palm J P, Graf P, Lundberg J O, Alving K. Characterization of exhaled nitric oxide: introducing a new reproducible method for nasal nitric oxide measurements.  Eur Respir J. 2000;  16 236-241
• 176 Schedin U, Frostell C, Persson M G, Jakobsson J, Andersson G, Gustafsson L E. Contribution from upper and lower airways to exhaled endogenous nitric oxide in humans.  Acta Anaesthesiol Scand. 1995;  39 327-332
• 177 Furukawa K, Harrison D G, Saleh D, Shennib H, Chagnon F P, Glaid A. Expression of nitric oxide synthase in the human nasal mucosa.  Am J Respir Crit Care Med. 1996;  153 847-850
• 178 Lundberg J O, Farkas-Szallasi T, Weitzberg E, Rinder J, Lidholm J, Anggaard A. et al . High nitric oxide production in human paranasal sinuses.  Nat Med. 1995;  1 370-373
• 179 Lundberg J O, Weitzberg E. Nasal nitric oxide in man.  Thorax. 1999;  54 947-952
• 180 Haddad I Y, Pataki G, Hu P, Galliani C, Beckman J S, Matalon S. Quantitation of nitrotyrosine levels in lung sections of patients and animals with acute lung injury.  J Clin Invest. 1994;  94 2407-2413
• 181 Feng X, Guo Z, Nourbakhsh M, Hauser H, Ganster R, Shao L. et al . Identification of a negative response element in the human inducible nitric-oxide synthase (hiNOS) promoter: The role of NF-κB-repressing factor (NRF) in basal repression of the hiNOS gene.  Proc Natl Acad Sci USA. 2002;  99 14 212-14 217
• 182 Aust A E, Ball J C, Hu A A, Lighty J S, Smith K R, Straccia A M. et al . Particle characteristics responsible for effects on human lung epithelial cells.  Res Rep Health Eff Inst. 2002;  110 1-65
• 183 Dreher K L, Jaskot R H, Lehmann J R, Richards J H, McGee J K, Ghio A J. et al . Soluble transition metals mediate residual oil fly ash induced acute lung injury.  J Toxicol Environ Health. 1997;  50 285-305
• 184 Frampton M W, Ghio A J, Samet J M, Carson J L, Carter J D, Devlin R B. Effects of aqueous extracts of PM(10) filters from the Utah valley on human airway epithelial cells.  Am J Physiol. 1999;  277 960-967
• 185 Himeno S, Yanagiya T, Enomoto S, Kondo Y, Imura N. Cellular cadmium uptake mediated by the transport system for manganese.  Tohoku J Exp Med. 2002;  196 43-50
• 186 Guerinot M L. The ZIP family of metal transporters.  Biochim Biophys Acta. 2000;  1465 190-198
• 187 Hubert N, Hentze M W. Previously uncharacterized isoforms of divalent metal transporter (DMT)-1: implications for regulation and cellular function.  Proc Natl Acad Sci USA. 2002;  99 12 345-12 350
• 188 Ghio A J, Stonehuerner J, Dailey L A, Carter J D. Metals associated with both the water-soluble and insoluble fractions of an ambient air pollution particle catalyze an oxidative stress.  Inhal Toxicol. 1999;  11 37-49
• 189 Stohs S J, Bagchi D. Oxidative mechanisms in the toxicity of metal ions.  Free Radic Biol Med. 1995;  18 321-336
• 190 Samet J M, Graves L M, Quay J, Dailey L A, Devlin R B, Ghio A J. et al . Activation of MAPKs in human bronchial epithelial cells exposed to metals.  Am J Physiol. 1998;  275 L551-L558
• 191 Bernstam L, Nriagu J. Molecular aspects of arsenic stress.  J Toxicol Environ Health B Crit Rev. 2000;  3 293-322
• 192 Zhou Y M, Zhong C Y, Kennedy I M, Leppert V J, Pinkerton K E. Oxidative stress and NFκB activation in the lungs of rats: a synergistic interaction between soot and iron particles.  Toxicol Appl Pharmacol. 2003;  190 157-169
• 193 Meriin A B, Yaglom J A, Gabai V L, Zon L, Ganiatsas S, Mosser D D. et al . Protein-damaging stresses activate c-Jun N-terminal kinase via inhibition of its dephosphorylation: a novel pathway controlled by HSP72.  Mol Cell Biol. 1999;  19 2547-2555
• 194 Cheng J Z, Sharma R, Yang Y, Singhal S S, Sharma A, Saini M K. et al . Accelerated metabolism and exclusion of 4-hydroxynonenal through induction of RLIP76 and hGST5.8 is an early adaptive response of cells to heat and oxidative stress.  J Biol Chem. 2001;  276 41 213-41 223
• 195 Marnett L J. Oxy radicals, lipid peroxidation and DNA damage.  Toxicology. 2002;  181 - 182 219-222
• 196 Kharbanda S, Pandey P, Yamauchi T, Kumar S, Kaneki M, Kumar V. et al . Activation of MEK Kinase 1 by the c-Abl Protein Tyrosine Kinase in Response to DNA Damage.  Mol Cell Biol. 2000;  20 4979-4989
• 197 Kyriakis J M, Avruch J. Sounding the alarm: protein kinase cascades activated by stress and inflammation.  J Biol Chem. 1996;  271 24 313-24 316
• 198 Gius D, Botero A, Shah S, Curry H A. Intracellular oxidation/reduction status in the regulation of transcription factors NF-κB and AP-1.  Toxicol Lett. 1999;  106 93-106
• 199 Schoonbroodt S, Piette J. Oxidative stress interference with the nuclear factor-κB activation pathways.  Biochem Pharmacol. 2000;  60 1075-1083
• 200 Bowie A, O'Neill L A. Oxidative stress and nuclear factor-κB activation: a reassessment of the evidence in the light of recent discoveries.  Biochem Pharmacol. 2000;  59 13-23
• 201 Schoonbroodt S, Ferreira V, Best-Belpomme M, Boelaert J R, Legrand-Poels S, Korner M. et al . Crucial role of the amino-terminal tyrosine residue 42 and the carboxyl-terminal PEST domain of I κB alpha in NF-κB activation by an oxidative stress.  J Immunol. 2000;  164 4292-4300
• 202 Byun M S, Jeon K I, Choi J W, Shim J Y, Jue D M. Dual effect of oxidative stress on NF-kappakB activation in HeLa cells.  Exp Mol Med. 2002;  34 332-339
• 203 Chandel N S, Trzyna W C, McClintock D S, Schumacker P T. Role of oxidants in NF-κB activation and TNF-alpha gene transcription induced by hypoxia and endotoxin.  J Immunol. 2000;  165 1013-1021
• 204 Hetland R B, Refsnes M, Myran T, Johansen B V, Uthus N, Schwarze P E. Mineral and/or metal content as critical determinants of particle-induced release of IL-6 and IL-8 from A549 cells.  J Toxicol Environ Health A. 2000;  60 47-65
• 205 Dong C, Davis R J, Flavell R A. Signaling by the JNK group of MAP kinases. c-jun N-terminal Kinase.  J Clin Immunol. 2001;  21 253-257
• 206 Li N, Kim S, Wang M, Froines J, Sioutas C, Nel A. Use of a stratified oxidative stress model to study the biological effects of ambient concentrated and diesel exhaust particulate matter.  Inhal Toxicol. 2002;  14 459-486
• 207 Kobayashi S D, Voyich J M, Buhl C L, Stahl R M, DeLeo F R. Global changes in gene expression by human polymorphonuclear leukocytes during receptor-mediated phagocytosis: Cell fate is regulated at the level of gene expression.  PNAS. 2002;  99 6901-6906
• 208 Beswick P H. Free radical activity of industrial fibers: role of iron in oxidative stress and activation of transcription factors.  Environ Health Perspect. 1997;  105 S (Suppl. 5) 1313-1317
• 209 Brown D M, Beswick P H, Donaldson K. Induction of nuclear translocation of NF-κB in epithelial cells by respirable mineral fibres.  J Pathol. 1999;  189 258-264
• 210 Brunekreef B, Janssen N A, de Hartog J, Harssema H, Knape M, van Vliet P. Air pollution from truck traffic and lung function in children living near motorways.  Epidemiology. 1997;  8 298-303
• 211 van Vliet P, Knape M, de Hartog J, Janssen N, Harssema H, Brunekreef B. Motor vehicle exhaust and chronic respiratory symptoms in children living near freeways.  Environ Res. 1997;  74 122-132
• 212 Kramer U, Koch T, Ranft U, Ring J, Behrendt H. Traffic-related air pollution is associated with atopy in children living in urban areas.  Epidemiology. 2000;  11 64-70
• 213 Nel A E, Diaz-Sanchez D, Ng D, Hiura T, Saxon A. Enhancement of allergic inflammation by the interaction between diesel exhaust particles and the immune system.  J Allergy Clin Immunol. 1998;  102 539-554
• 214 Diaz-Sanchez D, Garcia M P, Wang M, Jyrala M, Saxon A. Nasal challenge with diesel exhaust particles can induce sensitization to a neoallergen in the human mucosa.  J Allergy Clin Immunol. 1999;  104 1183-1188
• 215 Diaz-Sanchez D, Tsien A, Fleming J, Saxon A. Combined diesel exhaust particulate and ragweed allergen challenge markedly enhances human in vivo nasal ragweed-specific IgE and skews cytokine production to a T helper cell 2-type pattern.  J Immunol. 1997;  158 2406-2413
• 216 Diaz-Sanchez D, Dotson A R, Takenaka H, Saxon A. Diesel exhaust particles induce local IgE production in vivo and alter the pattern of IgE messenger RNA isoforms.  J Clin Invest. 1994;  94 1417-1425
• 217 Diaz-Sanchez D, Penichet-Garcia M, Saxon A. Diesel exhaust particles directly induce activated mast cells to degranulate and increase histamine levels and symptom severity.  J Allergy Clin Immunol. 2000;  106 1140-1146
• 218 Diaz-Sanchez D, Proietti L, Polosa R. Diesel fumes and the rising prevalence of atopy: an urban legend?.  Curr Allergy Asthma Rep. 2003;  3 146-152
• 219 Wang M, Saxon A, Diaz-Sanchez D. Early IL-4 production driving Th2 differentiation in a human in vivo allergic model is mast cell derived.  Clin Immunol. 1999;  90 47-54
• 220 Montnemery P, Popovic M, Andersson M, Greiff L, Nyberg P, Lofdahl C G. et al . Influence of heavy traffic, city dwelling and socio-economic status on nasal symptoms assessed in a postal population survey.  Respir Med. 2003;  97 970-977
• 221 Gluck U, Schutz R, Gebbers J O. Cytopathology of the nasal mucosa in chronic exposure to diesel engine emission: a five-year survey of Swiss customs officers.  Environ Health Perspect. 2003;  111 925-929
• 222 Li N, Wang M, Oberley T D, Sempf J M, Nel A E. Comparison of the pro-oxidative and proinflammatory effects of organic diesel exhaust particle chemicals in bronchial epithelial cells and macrophages.  J Immunol. 2002;  169 4531-4541
• 223 Diaz-Sanchez D, Tsien A, Casillas A, Dotson A R, Saxon A. Enhanced nasal cytokine production in human beings after in vivo challenge with diesel exhaust particles.  J Allergy Clin Immunol. 1996;  98 114-123
• 224 Diaz-Sanchez D, Jyrala M, Ng D, Nel A, Saxon A. In vivo nasal challenge with diesel exhaust particles enhances expression of the CC chemokines rantes, MIP-1alpha, and MCP-3 in humans.  Clin Immunol. 2000;  97 140-145
• 225 Meek M D. Ah receptor and estrogen receptor-dependent modulation of gene expression by extracts of diesel exhaust particles.  Environ Res. 1998;  79 114-121
• 226 Saeki K, Matsuda T, Kato T A, Yamada K, Mizutani T, Matsui S. et al . Activation of the human Ah receptor by aza-polycyclic aromatic hydrocarbons and their halogenated derivatives.  Biol Pharm Bull. 2003;  26 448-452
• 227 Gonzalez F J, Fernandez-Salguero P. The aryl hydrocarbon receptor. studies using the AHR-null mice.  Drug Metab Dispos. 1998;  26 1194-1198
• 228 Tian Y, Rabson A B, Gallo M A. Ah receptor and NF-κB interactions: mechanisms and physiological implications.  Chem Biol Interact. 2002;  141 97-115
• 229 Puga A, Barnes S J, Chang C, Zhu H, Nephew K P, Khan S A. et al . Activation of transcription factors activator protein-1 and nuclear factor-κB by 2,3,7,8-tetrachlorodibenzo-p-dioxin.  Biochem Pharmacol. 2000;  59 997-1005
• 230 Kim D W, Gazourian L, Quadri S A, Romieu-Mourez R, Sherr D H, Sonenshein G E. The RelA NF-κB subunit and the aryl hydrocarbon receptor (AhR) cooperate to transactivate the c-myc promoter in mammary cells.  Oncogene. 2000;  19 5498-5506
• 231 Tian Y, Ke S, Denison M, Rabson A B, Gallo M A. Ah Receptor and NF-κB interactions, a potential mechanism for dioxin toxicity.  Journal of Biological Chemistry. 1999;  274 510-515
• 232 Elizondo G, Fernandez-Salguero P, Sheikh M S, Kim G Y, Fornace A J, Lee K S. et al . Altered cell cycle control at the G2/M phases in aryl hydrocarbon receptor-null embryo fibroblast.  Mol Pharmacol. 2000;  57 1056-1063
• 233 Shimizu Y, Nakatsuru Y, Ichinose M, Takahashi Y, Kume H, Mimura J. et al . Benzo[a]pyrene carcinogenicity is lost in mice lacking the aryl hydrocarbon receptor.  PNAS. 2000;  97 779-782
• 234 Chan W K, Yao G, Gu Y Z, Bradfield C A. Cross-talk between the Aryl Hydrocarbon Receptor and Hypoxia Inducible Factor Signaling Pathways. Demonstration of competition and compensation.  Journal of Biological Chemistry. 1999;  274 12 115-12 123
• 235 Dertinger S D, Nazarenko D A, Silverstone A E, Gasiewicz T A. Aryl hydrocarbon receptor signaling plays a significant role in mediating benzo[a]pyrene- and cigarette smoke condensate-induced cytogenetic damage in vivo.  Carcinogenesis. 2001;  22 171-177
• 236 Dockery D W, Speizer F E, Stram D O, Ware J H, Spengler J D, Ferris B G Jr. Effects of inhalable particles on respiratory health of children.  Am Rev Respir Dis. 1989;  139 587-594
• 237 Cullen R T, Tran C L, Buchanan D, Davis J M, Searl A, Jones A D. et al . Inhalation of poorly soluble particles. I. Differences in inflammatory response and clearance during exposure.  Inhal Toxicol. 2000;  12 1089-1111
• 238 Donaldson K. Nonneoplastic lung responses induced in experimental animals by exposure to poorly soluble nonfibrous particles.  Inhal Toxicol. 2000;  12 121-139
• 239 Brown D M, Wilson M R, MacNee W, Stone V, Donaldson K. Size-dependent proinflammatory effects of ultrafine polystyrene particles: a role for surface area and oxidative stress in the enhanced activity of ultrafines.  Toxicol Appl Pharmacol. 2001;  175 191-199
• 240 Kobzik L. Lung macrophage uptake of unopsonized environmental particulates. Role of scavenger-type receptors.  J Immunol. 1995;  155 367-376
• 241 Obot C J, Morandi M T, Beebe T P, Hamilton R F, Holian A. Surface components of airborne particulate matter induce macrophage apoptosis through scavenger receptors.  Toxicol Appl Pharmacol. 2002;  184 98-106
• 242 Palecanda A, Paulauskis J, Al Mutairi E, Imrich A, Qin G, Suzuki H. et al . Role of the scavenger receptor MARCO in alveolar macrophage binding of unopsonized environmental particles.  The Journal of Experimental Medicine. 1999;  189 1497-1506
• 243 Palecanda A, Kobzik L. Receptors for unopsonized particles: the role of alveolar macrophage scavenger receptors.  Curr Mol Med. 2001;  1 589-595
• 244 Fraser I P, Ezekowitz R AB. Receptors for microbial products: Carbohydrates. In: Gallin JI, Snyderman R (eds) Inflammation basic principles and clinical correlates. Philadelphia, PA; Lippincott Williams & Wilkins 1999: 515-524
• 245 Stringer B, Imrich A, Kobzik L. Lung epithelial cell (A549) interaction with unopsonized environmental particulates: quantitation of particle-specific binding and IL-8 production.  Exp Lung Res. 1996;  22 495-508
• 246 Dunne D W, Resnick D, Greenberg J, Krieger M, Joiner K A. The type I macrophage scavenger receptor binds to gram-positive bacteria and recognizes lipoteichoic acid.  PNAS. 1994;  91 1863-1867
• 247 Elomaa O, Sankala M, Pikkarainen T, Bergmann U, Tuuttila A, Raatikainen-Ahokas A. et al . Structure of the human macrophage MARCO receptor and characterization of its bacteria-binding region.  J Biol Chem. 1998;  273 4530-4538
• 248 Goldsmith C A, Frevert C, Imrich A, Sioutas C, Kobzik L. Alveolar macrophage interaction with air pollution particulates.  Environ Health Perspect. 1997;  105 Suppl 5 1191-1195
• 249 Stringer B, Imrich A, Kobzik L. Flow cytometric assay of lung macrophage uptake of environmental particulates.  Cytometry. 1995;  20 23-32
• 250 Tao F, Palecanda A, Kumar S, Kobzik L. Generation of a monoclonal antibody that blocks epithelial binding of unopsonized particles.  Hybrid Hybridomics. 2003;  22 17-21
• 251 Riechelmann H, Rettinger G, Weschta M, Keck T, Deutschle T. Effects of low-toxicity particulate matter on human nasal function.  J Occup Environ Med. 2003;  45 54-60
• 252 Heinrich J. Nonallergic respiratory morbidity improved along with a decline of traditional air pollution levels: a review.  Eur Respir J Suppl. 2003;  40 64s-69s
• 253 von Mutius E, Sherrill D L, Fritzsch C, Martinez F D, Lebowitz M D. Air pollution and upper respiratory symptoms in children from East Germany.  Eur Respir J. 1995;  8 723-728
• 254 Peters A, Goldstein I F, Beyer U, Franke K, Heinrich J, Dockery D W. et al . Acute health effects of exposure to high levels of air pollution in eastern Europe.  Am J Epidemiol. 1996;  144 570-581
• 255 Peacock J L, Symonds P, Jackson P, Bremner S A, Scarlett J F, Strachan D P. et al . Acute effects of winter air pollution on respiratory function in schoolchildren in southern England.  Occup Environ Med. 2003;  60 82-89
• 256 Pikhart H, Bobak M, Gorynski P, Wojtyniak B, Danova J, Celko M A. et al . Outdoor sulphur dioxide and respiratory symptoms in Czech and Polish school children: a small-area study (SAVIAH). Small-area variation in air pollution and health.  Int Arch Occup Environ Health. 2001;  74 574-578
• 257 Knorst M M, Kienast K, Riechelmann H, Muller-Quernheim J, Ferlinz R. Effect of sulfur dioxide on mucociliary activity and ciliary beat frequency in guinea pig trachea.  Int Arch Occup Environ Health. 1994;  65 325-328
• 258 Kienast K, Riechelmann H, Knorst M, Schlegel J, Muller-Quernheim J, Schellenberg J. et al . An experimental model for the exposure of human ciliated cells to sulfur dioxide at different concentrations.  Clin Investig. 1994;  72 215-219
• 259 Gunnison A F, Sellakumar A, Currie D, Snyder E A. Distribution, metabolism and toxicity of inhaled sulfur dioxide and endogenously generated sulfite in the respiratory tract of normal and sulfite oxidase-deficient rats.  J Toxicol Environ Health. 1987;  21 141-162
• 260 Riechelmann H, Maurer J, Kienast K, Hafner B, Mann W J. Respiratory epithelium exposed to sulfur dioxide-functional and ultrastructural alterations.  Laryngoscope. 1995;  105 295-299
• 261 Ishizuka S, Yamaya M, Suzuki T, Nakayama K, Kamanaka M, Ida S. et al . Acid exposure stimulates the adherence of Streptococcus pneumoniae to cultured human airway epithelial cells: effects on platelet-activating factor receptor expression.  Am J Respir Cell Mol Biol. 2001;  24 459-468
• 262 Langley-Evans S C, Phillips G J, Jackson A A. Sulphur dioxide: a potent glutathione depleting agent.  Comp Biochem Physiol C Pharmacol Toxicol Endocrinol. 1996;  114 89-98
• 263 Lee W J, Teschke K, Kauppinen T, Andersen A, Jappinen P, Szadkowska-Stanczyk I. et al . Mortality from lung cancer in workers exposed to sulfur dioxide in the pulp and paper industry.  Environ Health Perspect. 2002;  110 991-995
• 264 Nyberg F, Gustavsson P, Jarup L, Bellander T, Berglind N, Jakobsson R. et al . Urban air pollution and lung cancer in Stockholm.  Epidemiology. 2000;  11 487-495
• 265 NN . Sulfur dioxide and some sulfites, bisulfites and metabisulfites.  IARC Monogr Eval Carcinog Risks Hum. 1992;  54 131-188
• 266 Tominaga M, Julius D. Capsaicin receptor in the pain pathway.  Jpn J Pharmacol. 2000;  83 20-24
• 267 Blomberg A, Krishna M T, Bocchino V, Biscione G L, Shute J K, Kelly F J. et al . The inflammatory effects of 2ppm NO2 on the airways of healthy subjects.  Am J Respir Crit Care Med. 1997;  156 418-424
• 268 Wang J H, Devalia J L, Duddle J M, Hamilton S A, Davies R J. Effect of six-hour exposure to nitrogen dioxide on early-phase nasal response to allergen challenge in patients with a history of seasonal allergic rhinitis.  J Allergy Clin Immunol. 1995;  96 669-676
• 269 Wang J H, Duddle J, Devalia J L, Davies R J. Nitrogen dioxide increases eosinophil activation in the early-phase response to nasal allergen provocation.  Int Arch Allergy Immunol. 1995;  107 103-105
• 270 Pryor W A, Squadrito G L, Friedman M. The cascade mechanism to explain ozone toxicity: the role of lipid ozonation products.  Free Radic Biol Med. 1995;  19 935-941
• 271 Pryor W A, Squadrito G L, Friedman M. A new mechanism for the toxicity of ozone.  Toxicol Lett. 1995;  83 287-293
• 272 Nichols B G, Woods J S, Luchtel D L, Corral J, Koenig J Q. Effects of ozone exposure on nuclear factor-κB activation and tumor necrosis factor-alpha expression in human nasal epithelial cells.  Toxicol Sci. 2001;  60 356-362
• 273 Frampton M W, Pryor W A, Cueto R, Cox C, Morrow P E, Utell M J. Ozone exposure increases aldehydes in epithelial lining fluid in human lung.  Am J Respir Crit Care Med. 1999;  159 1134-1137
• 274 Frampton M W, Pryor W A, Cueto R, Cox C, Morrow P E, Utell M J. Aldehydes (nonanal and hexanal) in rat and human bronchoalveolar lavage fluid after ozone exposure.  Res Rep Health Eff Inst. 1999;  90 1-15
• 275 Mustafa M G. Biochemical basis of ozone toxicity.  Free Radic Biol Med. 1990;  9 245-265
• 276 Long N C, Suh J, Morrow J D, Schiestl R H, Murthy G G, Brain J D. et al . Ozone causes lipid peroxidation but little antioxidant depletion in exercising and nonexercising hamsters.  J Appl Physiol. 2001;  91 1694-1700
• 277 Laskin D L, Fakhrzadeh L, Heck D E, Gerecke D, Laskin J D. Upregulation of phosphoinositide 3-kinase and protein kinase B in alveolar macrophages following ozone inhalation. Role of NF-κB and STAT-1 in ozone-induced nitric oxide production and toxicity.  Mol Cell Biochem. 2002;  234 - 235 91-98
• 278 Jaspers I, Flescher E, Chen L C. Ozone-induced IL-8 expression and transcription factor binding in respiratory epithelial cells.  Am J Physiol. 1997;  272 504-511
• 279 Haddad E B, Salmon M, Koto H, Barnes P J, Adcock I, Chung K F. Ozone induction of cytokine-induced neutrophil chemoattractant (CINC) and nuclear factor-kappa b in rat lung: inhibition by corticosteroids.  FEBS Lett. 1996;  379 265-268
• 280 Kafoury R M, Pryor W A, Squadrito G L, Salgo M G, Zou X, Friedman M. Lipid ozonation products activate phospholipases A2, C, and D.  Toxicol Appl Pharmacol. 1998;  150 338-349
• 281 Cho H Y, Hotchkiss J A, Bennett C B, Harkema J R. Neutrophil-dependent and neutrophil-independent alterations in the nasal epithelium of ozone-exposed rats.  Am J Respir Crit Care Med. 2000;  162 629-636
• 282 Schierhorn K, Hanf G, Fischer A, Umland B, Olze H, Kunkel G. Ozone-induced release of neuropeptides from human nasal mucosa cells.  Int Arch Allergy Immunol. 2002;  129 145-151
• 283 Wilkins C K, Wolkoff P, Clausen P A, Hammer M, Nielsen G D. Upper airway irritation of terpene/ozone oxidation products (TOPS). Dependence on reaction time, relative humidity and initial ozone concentration.  Toxicol Lett. 2003;  143 109-114
• 284 Potter-Perigo S, Kaplan E D, Luchtel D L, Baker C, Altman L C, Wight T N. Ozone alters the expression of tenascin-C in cultured primate nasal epithelial cells.  Am J Respir Cell Mol Biol. 1998;  18 471-478
• 285 Harkema J R, Hotchkiss J A, Griffith W C. Mucous cell metaplasia in rat nasal epithelium after a 20-month exposure to ozone: a morphometric study of epithelial differentiation.  Am J Respir Cell Mol Biol. 1997;  16 521-530
• 286 Harkema J R, Morgan K T, Gross E A, Catalano P J, Griffith W C. Consequences of prolonged inhalation of ozone on F344/N rats: collaborative studies. Part VII: Effects on the nasal mucociliary apparatus.  Res Rep Health Eff Inst. 1994;  65/7 3-26
• 287 Harkema J R, Catalano P J, Hotchkiss J A. Consequences of prolonged inhalation of ozone on F344/N rats: collaborative studies. Part XII: Atrophy of bone in nasal turbinates.  Res Rep Health Eff Inst. 1997;  65/12 1-19
• 288 Johnson N F, Hotchkiss J A, Harkema J R, Henderson R F. Proliferative responses of rat nasal epithelia to ozone.  Toxicol Appl Pharmacol. 1990;  103 143-155
• 289 Harkema J R, Barr E B, Hotchkiss J A. Responses of rat nasal epithelium to short- and long-term exposures of ozone: image analysis of epithelial injury, adaptation and repair.  Microsc Res Tech. 1997;  36 276-286
• 290 Harkema J R, Hotchkiss J A, Barr E B, Bennett C B, Gallup M, Lee J K. et al . Long-lasting effects of chronic ozone exposure on rat nasal epithelium.  Am J Respir Cell Mol Biol. 1999;  20 517-529
• 291 Jorge S A, Menck C F, Sies H, Osborne M R, Phillips D H, Sarasin A. et al . Mutagenic fingerprint of ozone in human cells.  DNA Repair (Amst). 2002;  1 369-378
• 292 Godish T. Aldehydes. In: Spengler JD, Samet JM, McCarthy JF (eds) Indoor air quality handbook. New York; McGraw-Hill 2001: 32.1-32.22
• 293 Tucker G. Volatile organic compounds. In: Spengler JD, Samet JM, McCarthy JF (eds) Indoor air quality handbook. New York; McGraw-Hill 2001: 31.1-31.20
• 294 Alarie Y. Sensory irritation of the upper airways by airborne chemicals.  Toxicol Appl Pharmacol. 1973;  24 279-297
• 295 Bos P M, Zwart A, Reuzel P G, Bragt P C. Evaluation of the sensory irritation test for the assessment of occupational health risk.  Crit Rev Toxicol. 1991;  21 423-450
• 296 Alarie Y, Nielsen G D, Schaper M M. Animal bioassays for evaluation of indoor air quality. In: Spengler JD, Samet JM, McCarthy JF (eds) Indoor air quality handbook. New York; McGraw-Hill 2001: 23.1-23.49
• 297 Severini C, Improta G, Falconieri-Erspamer G, Salvadori S, Erspamer V. The tachykinin peptide family.  Pharmacol Rev. 2002;  54 285-322
• 298 Shirasaki H, Asakura K, Narita S I, Kataura A. Expression of substance P (NK1) receptor mRNA in human nose.  Acta Otolaryngol. 1998;  118 717-722
• 299 Richardson J D, Vasko M R. Cellular mechanisms of neurogenic inflammation.  J Pharmacol Exp Ther. 2002;  302 839-845
• 300 Hunter D D, Satterfield B E, Huang J, Fedan J S, Dey R D. Toluene diisocyanate enhances substance P in sensory neurons innervating the nasal mucosa.  Am J Respir Crit Care Med. 2000;  161 543-549
• 301 Morris J B, Stanek J, Gianutsos G. Sensory nerve-mediated immediate nasal responses to inspired acrolein.  J Appl Physiol. 1999;  87 1877-1886
• 302 Sasamura T, Kuraishi Y. Peripheral and central actions of capsaicin and VR1 receptor.  Jpn J Pharmacol. 1999;  80 275-280
• 303 Veronesi B, Oortgiesen M. Neurogenic inflammation and particulate matter (PM) air pollutants.  Neurotoxicology. 2001;  22 795-810
• 304 Wu Z X, Satterfield B E, Dey R D. Substance P released from intrinsic airway neurons contributes to ozone-enhanced airway hyperresponsiveness in ferret trachea.  J Appl Physiol. 2003;  95 742-750
• 305 Canning B J. Potential role of tachykinins in inflammatory diseases.  J Allergy Clin Immunol. 1997;  99 579-582
• 306 Hood V C, Cruwys S C, Urban L, Kidd B L. Differential role of neurokinin receptors in human lymphocyte and monocyte chemotaxis.  Regul Pept. 2000;  96 17-21
• 307 van der Kleij H P, Kraneveld A D, Redegeld F A, Gerard N P, Morteau O, Nijkamp F P. The tachykinin NK1 receptor is crucial for the development of non-atopic airway inflammation and hyperresponsiveness.  Eur J Pharmacol. 2003;  476 249-255
• 308 Phillips J E, Hey J A, Corboz M R. Tachykinin NK3 and NK1 receptor activation elicits secretion from porcine airway submucosal glands.  British Journal of Pharmacology. 2003;  138 254-260
• 309 Nakajima Y, Tsuchida K, Negishi M, Ito S, Nakanishi S. Direct linkage of three tachykinin receptors to stimulation of both phosphatidylinositol hydrolysis and cyclic AMP cascades in transfected Chinese hamster ovary cells.  J Biol Chem. 1992;  267 2437-2442
• 310 Mechiche H, Koroglu A, Candenas L, Pinto F M, Birembaut P, Bardou M. et al . Neurokinins induce relaxation of human pulmonary vessels through stimulation of endothelial NK1 receptors.  J Cardiovasc Pharmacol. 2003;  41 343-355
• 311 Pedersen K E, Buckner C K, Meeker S N, Undem B J. Pharmacological examination of the neurokinin-1 receptor mediating relaxation of human intralobar pulmonary artery.  J Pharmacol Exp Ther. 2000;  292 319-325
• 312 Baluk P, Thurston G, Murphy T J, Bunnett N W, McDonald D M. Neurogenic plasma leakage in mouse airways.  Br J Pharmacol. 1999;  126 522-528
• 313 Quinlan K L, Naik S M, Cannon G, Armstrong C A, Bunnett N W, Ansel J C. et al . Substance P activates coincident NF-AT- and NF-κB-dependent adhesion molecule gene expression in microvascular endothelial cells through intracellular calcium mobilization.  J Immunol. 1999;  163 5656-5665
• 314 Baluk P, Bertrand C, Geppetti P, McDonald D M, Nadel J A. NK1 receptors mediate leukocyte adhesion in neurogenic inflammation in the rat trachea.  Am J Physiol. 1995;  268 L263-L269
• 315 DeRose V, Robbins R A, Snider R M, Spurzem J R, Thiele G M, Rennard S I. et al . Substance P increases neutrophil adhesion to bronchial epithelial cells.  J Immunol. 1994;  152 1339-1346
• 316 Kuo H P, Lin H C, Hwang K H, Wang C H, Lu L C. Lipopolysaccharide enhances substance P-mediated neutrophil adherence to epithelial cells and cytokine release.  Am J Respir Crit Care Med. 2000;  162 1891-1897
• 317 Tominaga K, Honda K, Akahoshi A, Makino Y, Kawarabayashi T, Takano Y. et al . Substance P causes adhesion of neutrophils to endothelial cells via protein kinase C.  Biol Pharm Bull. 1999;  22 1242-1245
• 318 Dianzani C, Collino M, Lombardi G, Garbarino G, Fantozzi R. Substance P increases neutrophil adhesion to human umbilical vein endothelial cells.  Br J Pharmacol. 2003;  139 1103-1110
• 319 Kahler C M, Pischel A, Kaufmann G, Wiedermann C J. Influence of neuropeptides on neutrophil adhesion and transmigration through a lung fibroblast barrier in vitro.  Exp Lung Res. 2001;  27 25-46
• 320 Tanabe T, Otani H, Bao L, Mikami Y, Yasukura T, Ninomiya T. et al . Intracellular signaling pathway of substance P-induced superoxide production in human neutrophils.  Eur J Pharmacol. 1996;  299 187-195
• 321 Bockmann S, Seep J, Jonas L. Delay of neutrophil apoptosis by the neuropeptide substance P: involvement of caspase cascade.  Peptides. 2001;  22 661-670
• 322 Hood V C, Cruwys S C, Urban L, Kidd B L. Differential role of neurokinin receptors in human lymphocyte and monocyte chemotaxis.  Regul Pept. 2000;  96 17-21
• 323 Dunzendorfer S, Kaser A, Meierhofer C, Tilg H, Wiedermann C J. Cutting edge: peripheral neuropeptides attract immature and arrest mature blood-derived dendritic cells.  J Immunol. 2001;  166 2167-2172
• 324 Numao T, Agrawal D K. Neuropeptides modulate human eosinophil chemotaxis.  The Journal of Immunology. 1992;  149 3309-3315
• 325 Dunzendorfer S, Schratzberger P, Reinisch N, Kahler C M, Wiedermann C J. Secretoneurin, a novel neuropeptide, is a potent chemoattractant for human eosinophils.  Blood. 1998;  91 1527-1532
• 326 Korsgren M, Erjefalt J S, Hinterholzl J, Fischer-Colbrie R, Ahlstrom Emanuelsson C, Andersson M. et al . Neural expression and increased lavage fluid levels of secretoneurin in seasonal allergic rhinitis.  Am J Respir Crit Care Med. 2003;  167 1504-1508
• 327 van der Kleij H P, Ma D, Redegeld F A, Kraneveld A D, Nijkamp F P, Bienenstock J. Functional expression of neurokinin 1 receptors on mast cells induced by IL-4 and stem cell factor.  J Immunol. 2003;  171 2074-2079
• 328 Lilly C M, Hall A E, Rodger I W, Kobzik L, Haley K J, Drazen J M. Substance P-induced histamine release in tracheally perfused guinea pig lungs.  J Appl Physiol. 1995;  78 1234-1241
• 329 Brass D M, Savov J D, Gavett S H, Haykal-Coates N, Schwartz D A. Subchronic endotoxin inhalation causes persistent airway disease.  Am J Physiol Lung Cell Mol Physiol. 2003;  285 L755-L761
• 330 Dube D, Puruckherr M, Byrd R P, Roy T M. Reactive airways dysfunction syndrome following metal fume fever.  Tenn Med. 2002;  95 236-238
• 331 Quirce S, Gala G, Perez-Camo I, Sanchez-Fernandez C, Pacheco A, Losada E. Irritant-induced asthma: clinical and functional aspects.  J Asthma. 2000;  37 267-274
• 332 Leroyer C, Malo J L, Girard D, Dufour J G, Gautrin D. Chronic rhinitis in workers at risk of reactive airways dysfunction syndrome due to exposure to chlorine.  Occup Environ Med. 1999;  56 334-338
• 333 Deschamps D, Questel F, Baud F J, Gervais P, Dally S. Persistent asthma after acute inhalation of organophosphate insecticide.  Lancet. 1994;  344 1712
• 334 Teramoto S, Tanaka H, Kaneko S, Abe S. Neurokinin-1 receptor antagonist inhibits short-term sulfuric-acid-induced airway hyperresponsiveness in sensitized guinea pigs.  Int Arch Allergy Immunol. 2000;  121 53-56
• 335 Castranova V, Frazer D G, Manley L K, Dey R D. Pulmonary alterations associated with inhalation of occupational and environmental irritants.  Int Immunopharmacol. 2002;  2 163-172
• 336 Sikora E R, Stone S, Tomblyn S, Frazer D G, Castranova V, Dey R D. Asphalt exposure enhances neuropeptide levels in sensory neurons projecting to the rat nasal epithelium.  J Toxicol Environ Health A. 2003;  66 1015-1027
• 337 Romero M I, Rangappa N, Li L, Lightfoot E, Garry M G, Smith G M. Extensive sprouting of sensory afferents and hyperalgesia induced by conditional expression of nerve growth factor in the adult spinal cord.  J Neurosci. 2000;  20 4435-4445
• 338 Bibel M, Barde Y A. Neurotrophins: key regulators of cell fate and cell shape in the vertebrate nervous system.  Genes Dev. 2000;  14 2919-2937
• 339 Braun A, Quarcoo D, Schulte-Herbruggen O, Lommatzsch M, Hoyle G, Renz H. Nerve growth factor induces airway hyperresponsiveness in mice.  Int Arch Allergy Immunol. 2001;  124 205-207
• 340 de Vries A, Dessing M, Engels F, Henricks P, Nijkamp F. Nerve growth factor induces a aeurokinin-1 receptor-mediated airway hyperresponsiveness in Guinea Pigs.  Am J Respir Crit Care Med. 1999;  159 1541-1544
• 341 Baraniuk J N, Ali M, Yuta A, Fang S Y, Naranch K. Hypertonic saline nasal provocation stimulates nociceptive nerves, substance P release, and glandular mucous exocytosis in normal humans.  Am J Respir Crit Care Med. 1999;  160 655-662
• 342 Sanico A M, Stanisz A M, Gleeson T D, Bora S, Proud D, Bienenstock J. et al . Nerve growth factor expression and release in allergic inflammatory disease of the upper airways.  Am J Respir Crit Care Med. 2000;  161 1631-1635
• 343 Kanda N, Watanabe S. Histamine enhances the production of nerve growth factor in human keratinocytes.  J Invest Dermatol. 2003;  121 570-577
• 344 Fox A J, Patel H J, Barnes P J, Belvisi M G. Release of nerve growth factor by human pulmonary epithelial cells: role in airway inflammatory diseases.  Eur J Pharmacol. 2001;  424 159-162
• 345 Lallemend F, Lefebvre P P, Hans G, Rigo J M, Van De Water T R, Moonen G. et al . Substance P protects spiral ganglion neurons from apoptosis via PKC-Ca²⁺-MAPK/ERK pathways.  J Neurochem. 2003;  87 508-521
• 346 Weyer U, Schafer R, Himmler A, Mayer S K, Burger E, Czernilofsky A P. et al . Establishment of a cellular assay system for G protein-linked receptors: coupling of human NK2 and 5-HT2 receptors to phospholipase C activates a luciferase reporter gene.  Receptor Channels. 1993;  1 193-200
• 347 Hoyle G W, Graham R M, Finkelstein J B, Nguyen K P, Gozal D, Friedman M. Hyperinnervation of the airways in transgenic mice overexpressing nerve growth factor.  Am J Respir Cell Mol Biol. 1998;  18 149-157
• 348 Lee K F, Li E, Huber L J, Landis S C, Sharpe A H, Chao M V. et al . Targeted mutation of the gene encoding the low affinity NGF receptor p75 leads to deficits in the peripheral sensory nervous system.  Cell. 1992;  69 737-749
• 349 Graham R M, Friedman M, Hoyle G W. Sensory nerves promote ozone-induced lung inflammation in mice.  Am J Respir Crit Care Med. 2001;  164 307-313
• 350 Tamaoki J, Chiyotani A, Tagaya E, Araake M, Nagai A. Airway hyper-responsiveness to neurokinin A and bradykinin following Mycoplasma pneumoniae infection associated with reduced epithelial neutral endopeptidase.  Microbiology. 1998;  144 ( Pt 9) 2481-2486
• 351 Rumsey W L, Aharony D, Bialecki R A, Abbott B M, Barthlow H G, Caccese R. et al . Pharmacological Characterization of ZD6021: A novel, orally active antagonist of the tachykinin receptors.  Journal of Pharmacology And Experimental Therapeutics. 2001;  298 307-315
• 352 Anthes J C, Chapman R W, Richard C, Eckel S, Corboz M, Hey J A. et al . SCH 206 272: a potent, orally active tachykinin NK(1), NK(2), and NK(3) receptor antagonist.  Eur J Pharmacol. 2002;  450 191-202
• 353 Korting H C, Schindler S, Hartinger A, Kerscher M, Angerpointner T, Maibach H I. MTT-assay and neutral red release (NRR)-assay: relative role in the prediction of the irritancy potential of surfactants.  Life Sci. 1994;  55 533-540
• 354 Mygind N. Nasal Allergy. 2nd ed. Oxford, London, Edinburgh, Boston, Melbourne; Blackwell Scientific Publications 1979
• 355 Benson V, Marano M A. Current estimates from the National Health Interview Survey, 1995.  Vital Health Stat. 1998;  10 1-428
• 356 Bauer S, Kirschning C J, Hacker H, Redecke V, Hausmann S, Akira S. et al . Human TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition.  PNAS. 2001;  98 9237-9242
• 357 Andrisani O M. CREB-mediated transcriptional control.  Crit Rev Eukaryot Gene Expr. 1999;  9 19-32
• 358 Shaulian E, Karin M. AP-1 as a regulator of cell life and death.  Nat Cell Biol. 2002;  4 E131-E136
• 359 Horsley V, Pavlath G K. NFAT: ubiquitous regulator of cell differentiation and adaptation.  J Cell Biol. 2002;  156 771-774
• 360 Chen F, Castranova V, Shi X, Demers L M. New insights into the role of nuclear factor-κB, a ubiquitous transcription factor in the initiation of diseases.  Clin Chem. 1999;  45 7-17

1 Ras und Raf1 sind Produkte von Genen, die im Falle einer Mutation die Tumorentstehung begünstigen können (Protoonkogene). Werden durch eine Mutation Ras- oder Raf1-Proteine gebildet, die stets aktiv sind, steht die Zelle unentwegt unter einem Wachstums- und Teilungsdruck.

2 Die grundsätzliche Möglichkeit, ein Gen in mRNA umzuschreiben, hängt vom Organisationszustand des Chromatins ab. Geringgradig kondensiertes Euchromatin kann transkribiert werden, während höhergradig kondensiertes Heterochromatin dem Transkriptionsapparat nicht zugänglich ist. Dieser Organisationszustand des Chromatins wird bei der Zellteilung auf die Tochterzelle weitergegeben. Dies erklärt, warum eine Basalzelle des Atemwegsepithels nicht plötzlich eine Nervenzelle hervorbringt [143].

3 Der Punkt neben dem Elementsymbol versinnbildlicht das ungepaarte Elektron des Radikals.