Macrophages in Innate and Acquired Immunity

Homer L. Twigg

doi:10.1055/s-2004-822302

Seminars in Respiratory and Critical Care Medicine, Inhaltsverzeichnis

Semin Respir Crit Care Med 2004; 25(1): 21-31
DOI: 10.1055/s-2004-822302

Macrophages in Innate and Acquired Immunity

Homer L. Twigg¹ III

¹Division of Pulmonary and Critical Care, Indiana University Medical Center, Indianapolis, Indiana

Abstract

Alveolar macrophages play a central role in pulmonary host defense. When foreign particles or pathogens enter the respiratory tract, constitutively present innate host defenses attempt to clear the challenge. Alveolar macrophage phagocytosis of foreign material is a critical component of this response, as is secretion of inflammatory mediators designed to combat invading pathogens. If the pathogenic burden is too large and overwhelms innate immunity, then acquired immune responses are initiated resulting in the generation of antigen-specific cellular and humoral immunity. In response to evolutionary pressures to minimize unnecessary inflammation in the lower respiratory tract, alveolar macrophages are generally poor accessory cells in the initiation of specific immunity. However, in many circumstances, especially those associated with cellular activation, alveolar macrophages can play an important role in the generation and expansion of pulmonary immune responses. This review discusses the role of alveolar macrophages in innate and acquired pulmonary host defense.

KEYWORDS

Alveolar macrophage - phagocytosis - immune response - cytokines

Volltext

Referenzen

REFERENCES

1 Thomas E, Ramberg R, Sale G. Direct evidence for a bone marrow origin of the alveolar macrophages in man. Science. 1976; 192 1016-1080
2 Bitterman P G, Saltzman L E, Adelberg S, Ferrans V J, Crystal R G. Alveolar macrophage replication: one mechanism for the expansion of the mononuclear phagocytes population in the chronically inflamed lung. J Clin Invest. 1984; 74 460-469
3 Spiteri M A, Clarke S W, Poulter L W. Isolation of phenotypically and functionally distinct macrophage subpopulations from human bronchoalveolar lavage. Eur Respir J. 1992; 5 717-726
4 Kradin R L, Sakamoto H, Preffer F I, Dombkowski D, Springer K M, Leary C P. Accumulation of macrophages with dendritic cell characteristics in the pulmonary response to Listeria . Am J Respir Crit Care Med. 2000; 161 535-542
5 Bell D, Young J W, Banchereau J. Dendritic cells. Adv Immunol. 1999; 72 255-324
6 Lee P T, Holt P G, McWilliam A S. Failure of MHC class II expression in neonatal alveolar macrophages: potential role of class II transactivator. Eur J Immunol. 2001; 31 2347-2356
7 Grigg J, Riedler J, Robertson C F, Boyle W, Uren S. Alveolar macrophage immaturity in infants and young children. Eur Respir J. 1999; 14 1198-1205
8 Lee P T, Holt P G, McWilliam A S. Role of alveolar macrophages in innate immunity in neonates: evidence for selective lipopolysaccharide binding protein production by rat neonatal alveolar macrophages. Am J Respir Cell Mol Biol. 2000; 23 652-661
9 Zissel G, Schlaak M, Muller-Quernheim J. Age-related decrease in accessory cell function of human alveolar macrophages. J Investig Med. 1999; 47 51-56
10 Corsini E, Viviani B, Lucchi L, Marinovich M, Racchi M, Galli C L. Ontogenesis of protein kinase C βII and its anchoring protein RACK1 in the maturation of alveolar macrophage functional responses. Immunol Lett. 2001; 76 89-93
11 Glasgow J E, Farrell B E, Fisher E S, Lauffenburger D A, Daniele R P. The motile response of alveolar macrophages. Am Rev Respir Dis. 1989; 139 320-329
12 Van Oss C J. Phagocytosis: an overview. Methods Enzymol. 1986; 132 3-15
13 O'Brien A D, Standiford T J, Christensen P J, Wilcoxen S E, Paine R. Chemotaxix of alveolar macrophages in response to signals derived from alveolar epithelial cells. J Lab Clin Med. 1998; 131 417-424
14 Wright J R, Youmas D C. Pulmonary surfactant protein A stimulates chemotaxis of alveolar macrophages. Am J Physiol. 1993; 264(Lung Cell Mol Physiol) L338-L344
15 Gordon S, Perry V H, Rabinowitz S, Chung L P, Rosen H. Plasma membrane receptors of the mononuclear phagocyte system. J Cell Sci. 1988; 9(suppl) 1-26
16 Kobzik L. Lung macrophage uptake of unopsonized environmental particulates: role of scavenger receptors. J Immunol. 1995; 155 367-376
17 van Crevel R, Ottenhoff T HM, van der Meer J WM. Innate immunity to Mycobacterium tuberculosis . Clin Microbiol Rev. 2002; 15 294-309
18 Pasula R, Wright J R, Kachel D L, Martin II W J. Surfactant protein A suppresses reactive nitrogen intermediates by alveolar macrophages in response to Mycobacterium tuberculosis . J Clin Invest. 1999; 103 483-490
19 Downing J F, Pasula R, Wright J R, Twigg H L, Martin II W J. Surfactant protein A promotes attachment of Mycobacterium tuberculosis to alveolar macrophages during infection with human immunodeficiency virus. Proc Natl Acad Sci USA. 1995; 92 4848-4852
20 Schagat T L, Wofford J A, Wright J R. Surfactant protein A enhances alveolar macrophage phagocytosis of apoptotic neutrophils. J Immunol. 2001; 166 2727-2733
21 Hu B, Sonstein J, Christensen P J, Punturieri A, Curtis J L. Deficient in vitro and in vivo phagocytosis of apoptotic T cells by resident murine alveolar macrophages. J Immunol. 2000; 165 2124-2133
22 Aggeler J, Werb Z. Initial events during phagocytosis by macrophages viewed from outside and inside the cell: membrane-particle interactions and clathrin. J Cell Biol. 1982; 94 613-623
23 Greenberg S, El Khoury J, Di Virgilio F, Kaplan E M, Silverstein S C. Ca²⁺-independent F-actin assembly and disassembly during Fc receptor-mediated phagocytosis in mouse macrophages. J Cell Biol. 1991; 113 757-767
24 Nathan C F. Secretion of oxygen intermediates; role in effector functions of activated macrophages. Fed Proc. 1982; 41 2206-2211
25 Liew F Y, Cos F EG. Nonspecific defence mechanism: the role of nitric oxide. Immunol Today. 1991; 12 A17-A21
26 Albina J E. On the expression of nitric oxide synthase by human macrophages. Why no NO. J Leukoc Biol. 1995; 58 643-649
27 Lekstrom-Himes J A, Gallin J I. Immunodeficiency diseases caused by defects in phagocytes. N Engl J Med. 2000; 343 1703-1714
28 Flynn J L, Chan J, Triebold K J, Dalton D K, Stewart T A, Bloom B R. An essential role for interferon gamma in resistance to Mycobacterium tuberculosis infection. J Exp Med. 1993; 178 2249-2254
29 Orme I M, Cooper A M. Cytokine/chemokine cascades in immunity to tuberculosis. Immunol Today. 1999; 20 307-312
30 Heldwein K A, Fenton M J. The role of Toll-like receptors in immunity against mycobacterial infection. Microbes Infect. 2002; 4 937-944
31 Keane J, Remold H G, Kornfeld H. Virulent Mycobacterium tuberculosis strains evade apoptosis of infected alveolar macrophages. J Immunol. 2000; 164 2016-2020
32 Mancuso P, Standiford T J, Marshall T, Peters-Golden M. 5-Lipoxygenase reaction products modulate alveolar macrophage phagocytosis of Klebsiella pneumoniae . Infect Immun. 1998; 66 5140-5146
33 Peters-Golden M, Coffey M. Role of leukotrienes in antimicrobial defense of the lung. J Lab Clin Med. 1998; 132 251-257
34 Coffey M J, Phare S M, Peters-Golden M. Prolonged exposure to lipopolysaccharide inhibits macrophage 5-lipoxygenase metabolism via induction of nitric oxide synthesis. J Immunol. 2000; 165 3592-3598
35 Rich E A, Panuska J R, Wallis R S, Wolf C B, Leonard M L, Ellner J J. Dyscoordinate expression of tumor necrosis factor-alpha by human blood monocytes and alveolar macrophages. Am Rev Respir Dis. 1989; 139 1010-1016
36 Iwamoto G K, Monick M M, Burmeister L F, Hunninghake G W. Interleukin 1 release by human alveolar macrophages and blood monocytes. Am J Physiol. 1989; 256(Cell Physiol 25) C1012-C1015
37 Toossi Z, Hirsch C S, Hamilton B P, Knuth C K, Friedlander M A, Rich E A. Decreased production TGF-beta 1 by human alveolar macrophages compared with blood monocytes. J Immunol. 1996; 156 3461-3468
38 Moore S A, Strieter R M, Rolfe M W, Standiford T J, Burdick M D, Kunkel S L. Expression and regulation of human alveolar macrophage-derived interleukin-1 receptor antagonist. Am J Respir Cell Mol Biol. 1992; 6 569-575
39 Martinet Y, Yamauchi K, Crystal R G. Differential expression of tumor necrosis factor/cachectin gene by blood and lung mononuclear phagocytes. Am Rev Respir Dis. 1988; 138 659-665
40 Strieter R M, Remick D G, Lynch J P et al.. Differential regulation of tumor necrosis factor-alpha in human alveolar macrophages and peripheral blood monocytes: a cellular and molecular analysis. Am J Respir Cell Mol Biol. 1989; 1 57-63
41 Standiford T J, Kunkel S L, Liebler J M, Burdick M D, Gilbert A R, Strieter R M. Gene expression of macrophage inflammatory protein-1α from human blood monocytes and alveolar macrophages is inhibited by interleukin-4. Am J Respir Cell Mol Biol. 1993; 9 192-198
42 Salez L, Balloy V, van Rooijen N et al.. Surfactant protein A suppresses lipopolysaccharide-induced IL-10 production by murine macrophages. J Immunol. 2001; 166 6376-6382
43 Soliman D M, Twigg H L. Cigarette smoking decreases bioactive interleukin-6 secretion by alveolar macrophages. Am J Physiol. 1992; 263(Lung Cell Mol Physiol) L471-L478
44 McRea K A, Ensor J E, Nall K, Bleecker E R, Hasday J D. Altered cytokine regulation in the lungs of cigarette smokers. Am J Respir Crit Care Med. 1994; 150 696-703
45 Standiford T J, Huffnagle G B. Cytokines in host defense against pneumonia. J Investig Med. 1997; 6 335-345
46 Martin T R. Overview of cytokine networks in lung injury. In: Pratter MR, Nelson S Cytokines and Pulmonary Infection Part II: The Role of Cytokines in Systemic and Pulmonary Medicine. ATS Continuing Education Monograph Series: New York, NY; American Lung Association 1997: 19-28
47 Weissler J C, Lipscomb M F, Lem V M, Toews G B. Tumor killing by human alveolar macrophages and blood monocytes. Am Rev Respir Dis. 1986; 134 532-537
48 Imaizumi K, Kawabe T, Ichiyama S et al.. Enhancement of tumoricidal activity of alveolar macrophages via CD40-CD40 ligand interaction. Am J Physiol. 1999; 277 L49-L57
49 Sauty A, Manuel J, Philippeaux M, Leuenberger P. Cytostatic activity of alveolar macrophages from smokers and nonsmokers: role of interleukin-1B, interleukin-6, and tumor necrosis factor-α. Am J Respir Cell Mol Biol. 1994; 11 631-637
50 Lauzon W, Lemaire I. Alveolar macrophage inhibition of lung-associated NK activity: involvement of prostaglandins and transforming growth factor-B₁ . Exp Lung Res. 1994; 20 331-349
51 Kaltreider H B, Curtis J L, Arraj S M. The mechanism of appearance of specific antibody-forming cells in the lungs of inbred mice after imunization with sheep erythrocytes intratracheally. Am Rev Respir Dis. 1987; 135 87-92
52 Curtis J L, Kaltreider H B. Characterization of bronchoalveolar lymphocytes during a specific antibody-forming cell response in the lungs of mice. Am Rev Respir Dis. 1989; 139 393-400
53 Toews G B, Vial W C, Dunn M M et al.. The accessory cell function of human alveolar macrophages in specific T cell proliferation. J Immunol. 1984; 132 181-186
54 Lipscomb M F, Lyons C R, Nunez G et al.. Human alveolar macrophages: HLA-DR-positive macrophages that are poor stimulators of a primary mixed leukocyte reaction. J Immunol. 1986; 136 497-504
55 Lyons C R, Ball E J, Toews G B, Weissler J C, Stastny P, Lipscomb M F. Inability of human alveolar macrophages to stimulate resting T cells correlates with decreased antigen-specific T cell-macrophage binding. J Immunol. 1986; 137 1173-1180
56 Holt P G, Oliver J, Bilyk N et al.. Downregulation of the antigen-presenting cell functions(s) of pulmonary dendritic cells in vivo by resident alveolar macrophages. J Exp Med. 1993; 177 397-407
57 Ferro T J, Monos D S, Spear B T. Carbohydrate differences in HLA-DR molecules synthesized by alveolar macrophages and blood monocytes. Am Rev Respir Dis. 1987; 135 1340-1344
58 Rich E A, Tweardy D J, Fujiwara H, Ellner J J. Spectrum of immunoregulatory functions and properties of human alveolar macrophages. Am Rev Respir Dis. 1987; 136 258-265
59 Denham S, Rowland I J. Inhibition of the reactive proliferation of lymphocytes by activated mcrophages: the role of nitric oxide. Clin Exp Immunol. 1992; 87 157-162
60 Thomassen M J, Buhrow L T, Connors M J, Kaneko T, Erzurum S C, Kavuru M S. Nitric oxide inhibits inflammatory cytokine production by human alveolar macrophages. Am J Respir Cell Mol Biol. 1997; 17 279-283
61 Bingisser R M, Tilbrook P A, Holt P G, Kees U R. Macrophage-derived nitric oxide regulates T cell activation via reversible disruption of the Jak3/STAT5 signaling pathway. J Immunol. 1998; 160 5729-5734
62 Yarbrough Jr W C, Wilkes D S, Weissler J C. Human alveolar macrophages inhibit receptor-mediated increases in intracellular calcium concentration in lymphocytes. Am J Respir Cell Mol Biol. 1991; 5 411-415
63 Chelen C J, Yu F, Feeman G J et al.. Human alveolar macrophages present antigen ineffectively due to defective expression of B7 costimulatory cell surface molecules. J Clin Invest. 1995; 95 1415-1421
64 Strickland D, Kees U R, Holt P G. Regulation of T-cell activation in the lung: alveolar macrophages induce reversible T-cell anergy in vitro associated with inhibition of interleukin-2 receptor signal transduction. Immunology. 1996; 87 250-258
65 Saltini C, Kirby M, Trapnell B C, Tamura N, Crystal R G. Biased accumulation of T lymphocytes with “memory”-type CD45 leukocyte common antigen gene expression on the epithelial surface of the human lung. J Exp Med. 1990; 171 1123-1140
66 Balaji K N, Schwander S K, Rich E A, Boom W H. Alveolar macrophages as accessory cells for human γδ T cells activated by Mycobacterium tuberculosis . J Immunol. 1995; 154 5959-5968
67 Vecchiarelli A, Dottorini M, Pietrella D et al.. Role of human alveolar macrophages as antigen-presenting cells in Cryptococcus neoformans infection. Am J Respir Cell Mol Biol. 1994; 11 130-137
68 Holt P G. Antigen presentation in the lung. Am J Respir Crit Care Med. 2000; 162 S151-S156
69 Banchereau J, Briere F, Caux C et al.. Immunobiology of dendritic cells. Annu Rev Immunol. 2000; 18 767-811
70 Zissel G, Ernst M, Schlaak M. Muller-Quernheim: accessory function of alveolar macrophages from patients with sarcoidosis and other granulomatous and nongranulomatous lung diseases. J Investig Med. 1997; 45 75-86
71 Nicod L P, Isler P. Alveolar macrophages in sarcoidosis coexpress high levels of CD86 (B7.2), CD40, and CD30L. Am J Respir Cell Mol Biol. 1997; 17 91-96
72 Somoskovi A, Zissel G, Ziegenhagen M W, Schlaak M, Muller-Quernheim J. Accessory function and costimulatory molecule expression of alveolar macrophages in patients with tuberculosis. Immunobiology. 2000; 201 450-460
73 Twigg H L, Iwamoto G K, Soliman D M. Role of cytokines in alveolar macrophage accessory cell function in HIV-infected individuals. J Immunol. 1992; 149 1462-1469
74 Agostini C, Facco M, Chilosi M, Semenzato G. Alveolar macrophage-T cell interactions during Th1-type sarcoid inflammation. Microsc Res Tech. 2001; 53 278-287
75 Bilyk N, Holt P G. Inhibition of the immunosuppressive activity of resident pulmonary alveolar macrophages by granulocyte/macrophage colony-stimulating factor. J Exp Med. 1993; 177 1773-1777
76 Weissler J C, Mendelson C, Moya F, Yarbrough Jr W C. Effect of insterstitial lung disease macrophages on T-cell signal transduction. Am J Respir Crit Care Med. 1994; 149 191-196
77 Tang C, Inman M D, van Rooijen N et al.. Th type 1-stimulating activity of lung macrophages inhibits Th2-mediated allergic airway inflammation by an IFN-γ-dependent mechanism. J Immunol. 2001; 166 1471-1481
78 Tang C, Ward C, Reid D, Bish R, O'Byrne P M, Walters E H. Normally suppressing CD40 coregulatory signals delivered by airway macrophages to Th2 lymphocytes are defective in patients with atopic asthma. J Allergy Clin Immunol. 2001; 107 863-870
79 Wilkes D S, Yarbrough W C, Weissler J C. Human alveolar macrophages inhibit immunoglobulin production in response to direct B cell mitogen. Am J Respir Cell Mol Biol. 1993; 9 141-147
80 Bauer W, Gorny N K, Baumann H R, Morell A. T-lymphocyte subsets and immunoglobulin concentrations in bronchoalveolar lavage of patients with sarcoidosis and high and low intensity alveolitis. Am Rev Respir Dis. 1985; 132 1060-1065
81 Wilkes D S, Weissler J C. Alloantigen-induced immunoglobulin production in human lung: differential effects of accessory cell populations on IgG synthesis. Am J Respir Cell Mol Biol. 1994; 10 339-346
82 MacLean J A, Xia W, Pinto C E, Zhao L, Liu H-W, Kradin R L. Sequestration of inhaled particulate antigens by lung phagocytes: a mechanism for the effective inhibition of pulmonary cell-mediated immunity. Am J Pathol. 1996; 148 657-666
83 Wijburg O LC, DiNatale S, Vadolas J, van Rooijen N, Strugnell R A. Alveolar macrophage regulate the induction of primary cytoxic T-lymphocyte responses during influenza virus infection. J Virol. 1997; 71 9450-9457
84 Debrick J E, Campbell P A, Staerz U D. Macrophages as accessory cells for class I MHC-restricted immune responses. J Immunol. 1991; 147 2846-2851
85 Quentmeier H, Klaucke J, Muhlradt F P, Drexler H G. Role of IL-6, IL-2, and IL-4 in the in vitro induction of cytotoxic T cells. J Immunol. 1992; 149 3316-3320
86 Plata F, Autran B, Martins L P et al.. AIDS virus-specific cytotoxic T lymphocytes in lung disorders. Nature. 1987; 328 348-351
87 Lee W C, McConnell I, Blacklaws B A. Cytotoxic activity against Maedi-visna virus-infected macrophages. J Virol. 1994; 68 8331-8338
88 Bingisser R, Stey C, Weller M, Groscurth P, Russi E, Frei K. Apoptosis in human alveolar macrophages is induced by endotoxin and is modulated by cytokines. Am J Respir Cell Mol Biol. 1996; 15 64-70

Homer L Twigg IIIM.D.

Indiana University Medical Center

1481 West 10th St., 111P-IU

Indianapolis, IN 46202

eMail: htwig@iupui.edu