Die Auswirkungen von Tabakrauch auf Alveolarmakrophagen – ein In-vivo-Kurzzeitrauchmodell zur Mauslunge

Zusammenfassung

Hintergrund: Der Einfluss von Tabakrauch auf das Phagozytoseverhalten von Alveolarmakrophagen in vivo wird kontrovers diskutiert. Bisherige Studien konnten diese Fragestellung nur in In-vitro-Modellen beantworten. Das vorgestellte Modell ist das erste In-vivo-Modell zu dieser Fragestellung.

Fragestellung: Verstärkt oder hemmt Tabakrauch die phagozytotische Aktivität von Alveolarmakrophagen bzw. führt Tabakrauch zu einem Anstieg der Alveolarmakrophagen?

Ergebnisse: Tabakrauch führt zu einer tendenziell verstärkten Aktivität von Alveolarmakrophagen.

Methodik: Die Intravitalmikroskopie der Lunge erlaubt die Beobachtung von Alveolarmakrophagen nahe der Lungenoberfläche.

Ergebnisse: Tabakrauch führt tendenziell zu einer vermehrten Phagozytose von Partikeln durch Alveolarmakrophagen und neutrophile Granulozyten.

Schlussfolgerung: Diese Studie unterstützt Untersuchungen, die in vitro keine Hemmung der phagozytotischen Aktivität von Alveolarmakrophagen nach Tabakrauchexposition zeigen konnten.

Abstract

Background: The effect of cigarette smoke (CS) on the phagocytosis of alveolar macrophages is discussed controversially on the basis of in vitro experiments. In this short report we describe the in vivo observations that we have performed.

Methods: For this purpose mice were exposed to CS for three consecutive days. One day later the fluorescent microspheres were administered intratracheally and the lung surface was investigated using long-distance fluorescence microscopy.

Results: We found that the numbers of neutrophils which engulfed particles was increased in the CS group as compared to controls. The overall phagocytic activity was not significantly different after CS exposure.

Conclusions: In conclusion the phagocytosis of alveolar macrophages and neutrophils after short time CS exposure was not affected. Further investigations will need to look for the effects of long-term CS exposure and the phagocytosis of living bacteria.

• Literatur

• 1 Prevot G, Plat G, Mazieres J. [COPD and lung cancer: epidemiological and biological links]. Rev Mal Respir 2012; 29: 545-556
• 2 Lopez AD, Murray CC. The global burden of disease, 1990 – 2020. Nat Med 1998; 4: 1241-1243
• 3 Barnes PJ. Chronic obstructive pulmonary disease. N Engl J Med 2000; 343: 269-280
• 4 Hoffmann D, Hoffmann I, El-Bayoumy K. The less harmful cigarette: a controversial issue. a tribute to Ernst L. Wynder. Chem Res Toxicol 2001; 14: 767-790
• 5 Smith CJ, Perfetti TA, Garg R et al. Percutaneous penetration enhancers in cigarette mainstream smoke. Food Chem Toxicol 2004; 42: 9-15
• 6 Gan WQ, Man SPF, Senthilselvan A et al. Association between chronic obtructive pulmonary disease und systemic inflammation: a systemic review and a metaanalysis. 2004; 59: 574-580
• 7 Blusse van Oud Albas A, Van der Linden-Schrever B, van Furth R. Origin and kinetics of pulmonary macrophages during inflammatory reactioninduced by intra-alveolar administration of aerosolized heat-killed BCG. Am Rev Respir Dis 1983; 128: 276-281
• 8 Mehta H, Nazzal K, Sadikot RT. Cigarette smoking and innate immunity. Inflamm Res 2008; 57: 497-503
• 9 Doyle I, Ratcliffe M, Walding A et al. Differential gene expression analysis in human monocyte-derived macrophages: impact of cigarette smoke on host defence. Mol Immunol 2010; 47: 1058-1065
• 10 Retamales I, Elliott WM, Meshi B et al. Amplification of inflammation in emphysema and its association with latent adenoviral infection. Am J Respir Crit Care Med 2001; 164: 469-473
• 11 Barnes PJ. Alveolar Macrophages as orchestrators of COPD. J COPD 2004; 1: 59-70
• 12 Shapiro SD. The macrophage in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1999; 160: S29-S32
• 13 Fadok VA, Bratton DL, Rose DM et al. A receptor for phosphatidylserine-specific clearance of apoptotic cells. Nature 2000; 405: 85-90
• 14 Russell RE, Thorley A, Culpitt SV et al. Alveolar macrophages-mediated elastolysis: the role of matrix metalloprteinases, cysteine and serine proteases. Am J Physiol Lung Cell Mol Physiol 2000; 283: L867-L873
• 15 Punturieri A, Filippov S, Allen E et al. Regulation of elastinolytic cysteine proteinase activity in normal and cathepsin K-deficient human macrophages. J Exp Med 2000; 192: 789-800
• 16 Ahn C, Mulligan P, Salcido RS. Smoking – the bane of wound healing: biomedical interventions and social influences. Adv Skin Wound Care 2008; 21: 227-236
• 17 Guo S, Dipietro LA. Factors affecting wound healing. J Dent Res 2010; 89: 219-229
• 18 Piao WH, Campagnolo D, Dayao C et al. Nicotine and inflammatory neurological disorders. Acta Pharmacol Sin 2009; 30: 715-722
• 19 Murin S, Bilello KS. Respiratory tract infections: another reason not to smoke. Cleve Clin J Med 2005; 72: 916-920
• 20 Arcavi L, Benowitz NL. Cigarette smoking and infection. Arch Intern Med 2004; 164: 2206-2216
• 21 Linder JA, Sim I. Antibiotic treatment of acute bronchitis in smokers: a systematic review. J Gen Intern Med 2002; 17: 230-234
• 22 Straus WL, Plouffe JF, File TM et al. Risk factors for domestic acquisition of legionnaires disease. Ohio legionnaires Disease Group. Arch Intern Med 1996; 156: 1685-1692
• 23 Shea JW, Huber GL, Holmes L et al. The effect of experimental tobacco smoke inhalation on in vitro alveolar macrophage bactericidal function. J Lab Clin Med 1978; 92: 270-282
• 24 McMaster SK, Paul-Clark MJ, Walters M et al. Cigarette smoke inhibits macrophage sensing of Gram-negative bacteria and lipopolysaccharide: relative roles of nicotine and oxidant stress. Br J Pharmacol 2008; 153: 536-543
• 25 Maity PC, Bhattacharjee S, Majumdar S et al. Potentiation by cigarette smoke of macrophage function against Leishmania donovani infection. Inflamm Res 2009; 58: 22-29
• 26 Stämpfli MR, Anderson GP. How cigarette smoke skews response to promote infection lung disease and cancer. Nat Rev Immunol 2009; 9: 377-384
• 27 Sopori M. Effects of cigarette smoke on the immune system. Nat Rev Immunol 2002; 2: 372-377
• 28 Thatcher TH, Benson RP, Phipps RP et al. High-dose but not low-dose mainstream cigarette smoke suppresses allergic airway inflammation by inhibiting T cell function. Am J Physiol Lung Cell Mol Physiol 2008; 295: L412-L421
• 29 Scott DA, Singer DL. Suppression of overt gingival inflammation in tobacco smokers – clinical and mechanistic considerations. Int J Dent Hyg 2004; 2: 104-110
• 30 Tschernig T, Veith NT, Schramm R et al. Direct visualisation of micro-particles in the living lung. 2012. eingereicht
• 31 Dziarski R et al. Binding of bacterial peptidoglycan to CD14. J Biol Chem 1998; 15: 8680-8690
• 32 Harris JO, Swenson EW, Johnson 3rd JE. Human alveolar macrophages: comparison of phagocytic ability, glucose utilization, and ultrastructure in smokers and nonsmokers. J Clin Invest 1970; 49: 2086-2096
• 33 Marquardt A, Halle S, Seckert CK et al. Single cell detection of latent cytomegalovirus reactivation in host tissue. J Gen Virol 2011; 92: 1279-1291
• 34 Bauer CM, Zavitz CC, Botelho FM et al. Treating viral exacerbations of chronic obstructive pulmonary disease: insights from a mouse model of cigarette smoke and H1N1 influenza infection. PLoS One 2010; 5: e13251