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. 1980 Apr;35:21–28. doi: 10.1289/ehp.803521

Macrophage damage in relation to the pathogenesis of lung diseases.

J D Brain
PMCID: PMC1568469  PMID: 6997029

Abstract

Pulmonary macrophages are important since their migratory patterns and behavior are often pivotal events in the pathogenesis of pulmonary disease. Alveolar macrophages act to decrease the probability of particle penetration through epithelial barriers, and their phagocytic and lytic potentials provide most of the known bactericadal properties of the lung. Macrophages are also involved in immune responses and in defense against neoplasms. Increased inert or infectious particles stimulate the recruitment of additional macrophages. Most free cells containing particles eventually reach the airways and are quickly carried to the pharynx and swallowed. In addition, evidence has now accumulated that macrophages play a part in the pathogenesis of pulmonary diseases. For example, the ingestion of some particles by macrophages causes a release of lysosomal enzymes into the macrophage cytoplasm. These enzymes may kill the macrophage, and dead or dying macrophages release a substance with attracts fibroblasts that elicit fibrogenic responses. Other toxic particles, such as cigarette smoke, my lead to a release of proteases and other toxic enzymes. All particles are capable of competitive inhibition of phagocytosis in macrophages and many may be cytotoxic and further depress phagocytosis. In addition, connective tissue macrophages may contribute to lung disease by concentrating and storing potent carcinogens or other toxic particles close to a reactive bronchial epithelium for long periods. Thus, even through macrophages serve as a first line of defense for the alveolar surface, they may also be capable of injuring the host while exercising their defensive role.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Allison A. C., Harington J. S., Birbeck M. An examination of the cytotoxic effects of silica on macrophages. J Exp Med. 1966 Aug 1;124(2):141–154. doi: 10.1084/jem.124.2.141. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Brain J. D., Golde D. W., Green G. M., Massaro D. J., Valberg P. A., Ward P. A., Werb Z. Biologic potential of pulmonary macrophages. Am Rev Respir Dis. 1978 Aug;118(2):435–443. doi: 10.1164/arrd.1978.118.2.435. [DOI] [PubMed] [Google Scholar]
  3. Burrell R., Anderson M. The induction of fibrogenesis by silica-treated alveolar macrophages. Environ Res. 1973 Dec;6(4):389–394. doi: 10.1016/0013-9351(73)90054-6. [DOI] [PubMed] [Google Scholar]
  4. COHN Z. A., WIENER E. THE PARTICULATE HYDROLASES OF MACROPHAGES. I. COMPARATIVE ENZYMOLOGY, ISOLATION, AND PROPERTIES. J Exp Med. 1963 Dec 1;118:991–1008. doi: 10.1084/jem.118.6.991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Evans R., Alexander P. Cooperation of immune lymphoid cells with macrophages in tumour immunity. Nature. 1970 Nov 14;228(5272):620–622. doi: 10.1038/228620a0. [DOI] [PubMed] [Google Scholar]
  6. Franson R. C., Waite M. Lysosomal phospholipase A 1 and A 2 of normal and bacillus calmette guerin-induced alveolar macrophages. J Cell Biol. 1973 Mar;56(3):621–627. doi: 10.1083/jcb.56.3.621. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. GORER P. A. Some recent work on tumor immunity. Adv Cancer Res. 1956;4:149–186. doi: 10.1016/s0065-230x(08)60724-1. [DOI] [PubMed] [Google Scholar]
  8. GREEN G. M., KASS E. H. THE ROLE OF THE ALVEOLAR MACROPHAGE IN THE CLEARANCE OF BACTERIA FROM THE LUNG. J Exp Med. 1964 Jan 1;119:167–176. doi: 10.1084/jem.119.1.167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gee J. B., Bodel P. T., Zorn S. K., Hinman L. M., Stevens C. A., Matthay R. A. Sarcoidosis and mononuclear phagocytes. Lung. 1978;155(3):243–253. doi: 10.1007/BF02730696. [DOI] [PubMed] [Google Scholar]
  10. Golde D. W., Territo M., Finley T. N., Cline M. J. Defective lung macrophages in pulmonary alveolar proteinosis. Ann Intern Med. 1976 Sep;85(3):304–309. doi: 10.7326/0003-4819-85-3-304. [DOI] [PubMed] [Google Scholar]
  11. Granger G. A., Weiser R. S. Homograft target cells: contact destruction in vitro by immune macrophages. Science. 1966 Jan 7;151(3706):97–99. doi: 10.1126/science.151.3706.97. [DOI] [PubMed] [Google Scholar]
  12. Hance A. J., Crystal R. G. The connective tissue of lung. Am Rev Respir Dis. 1975 Nov;112(5):657–711. doi: 10.1164/arrd.1975.112.5.657. [DOI] [PubMed] [Google Scholar]
  13. Harington J. S., Ritchie M., King P. C., Miller K. The in-vitro effects of silica-treated hamster macrophages on collagen production by hamster fibroblasts. J Pathol. 1973 Jan;109(1):21–37. doi: 10.1002/path.1711090104. [DOI] [PubMed] [Google Scholar]
  14. Heppleston A. G., Styles J. A. Activity of a macrophage factor in collagen formation by silica. Nature. 1967 Apr 29;214(5087):521–522. doi: 10.1038/214521a0. [DOI] [PubMed] [Google Scholar]
  15. Hocking W. G., Golde D. W. The pulmonary-alveolar macrophage (first of two parts). N Engl J Med. 1979 Sep 13;301(11):580–587. doi: 10.1056/NEJM197909133011104. [DOI] [PubMed] [Google Scholar]
  16. Hocking W. G., Golde D. W. The pulmonary-alveolar macrophage (second of two parts). N Engl J Med. 1979 Sep 20;301(12):639–645. doi: 10.1056/NEJM197909203011205. [DOI] [PubMed] [Google Scholar]
  17. Johanson W. G., Jr, Pierce A. K. Effects of elastase, collagenase, and papain on structure and function of rat lungs in vitro. J Clin Invest. 1972 Feb;51(2):288–293. doi: 10.1172/JCI106813. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kaplan P. D., Kuhn C., Pierce J. A. The induction of emphysema with elastase. I. The evolution of the lesion and the influence of serum. J Lab Clin Med. 1973 Sep;82(3):349–356. [PubMed] [Google Scholar]
  19. Keller R. Mechanisms by which activated normal macrophages destroy syngeneic rat tumour cells in vitro. Cytokinetics, non-involvement of T lymphocytes, and effect of metabolic inhibitors. Immunology. 1974 Aug;27(2):285–298. [PMC free article] [PubMed] [Google Scholar]
  20. Kuhn C., 3rd, Senior R. M. The role of elastases in the development of emphysema. Lung. 1978;155(3):185–197. [PubMed] [Google Scholar]
  21. LEAKE E. S., GONZALEZ-OJEDA D., MYRVIK Q. N. ENZYMATIC DIFFERENCES BETWEEN NORMAL ALVEOLAR MACROPHAGES AND OIL-INDUCED PERITONEAL MACROPHAGES OBTAINED FROM RABBITS. Exp Cell Res. 1964 Feb;33:553–561. doi: 10.1016/0014-4827(64)90020-5. [DOI] [PubMed] [Google Scholar]
  22. Leibovich S. J., Ross R. A macrophage-dependent factor that stimulates the proliferation of fibroblasts in vitro. Am J Pathol. 1976 Sep;84(3):501–514. [PMC free article] [PubMed] [Google Scholar]
  23. Levy M. H., Wheelock E. F. The role of macrophages in defense against neoplastic disease. Adv Cancer Res. 1974;20:131–163. doi: 10.1016/s0065-230x(08)60110-4. [DOI] [PubMed] [Google Scholar]
  24. Lieberman J., Gawad M. A. Inhibitors and activators of leukocytic proteases in purulent sputum. Digestion of human lung and inhibition by alpha 1-antitrypsin. J Lab Clin Med. 1971 May;77(5):713–727. [PubMed] [Google Scholar]
  25. Lieberman J. Involvement of leukocytic proteases in emphysema and antitrypsin deficiency. Arch Environ Health. 1973 Sep;27(3):196–200. doi: 10.1080/00039896.1973.10666351. [DOI] [PubMed] [Google Scholar]
  26. Maroudas N. G. Chemical and mechanical requirements for fibroblast adhesion. Nature. 1973 Aug 10;244(5415):353–354. doi: 10.1038/244353a0. [DOI] [PubMed] [Google Scholar]
  27. Mass B., Ikeda T., Meranze D. R., Weinbaum G., Kimbel P. Induction of experimental emphysema. Cellular and species specificity. Am Rev Respir Dis. 1972 Sep;106(3):384–391. doi: 10.1164/arrd.1972.106.3.384. [DOI] [PubMed] [Google Scholar]
  28. Pratt S. A., Smith M. H., Ladman A. J., Finley T. N. The ultrastructure of alveolar macrophages from human cigarette smokers and nonsmokers. Lab Invest. 1971 May;24(5):331–338. [PubMed] [Google Scholar]
  29. Rodriguez R. J., White R. R., Senior R. M., Levine E. A. Elastase release from human alveolar macrophages: comparison between smokers and nonsmokers. Science. 1977 Oct 21;198(4314):313–314. doi: 10.1126/science.910131. [DOI] [PubMed] [Google Scholar]
  30. Ross R., Everett N. B., Tyler R. Wound healing and collagen formation. VI. The origin of the wound fibroblast studied in parabiosis. J Cell Biol. 1970 Mar;44(3):645–654. doi: 10.1083/jcb.44.3.645. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Snider G. L., Hayes J. A., Franzblau C., Kagan H. M., Stone P. S., Korthy A. L. Relationship between elastolytic acitivity and experimental emphysema-induced properties of papain preparations. Am Rev Respir Dis. 1974 Sep;110(3):254–262. doi: 10.1164/arrd.1974.110.3.254. [DOI] [PubMed] [Google Scholar]
  32. Sorber W. A., Leake E. S., Myrvik Q. N. Isolation and characterization of hydrolase-containing granules from rabbit lung macrophages. J Reticuloendothel Soc. 1974 Sep;16(3):184–192. [PubMed] [Google Scholar]
  33. Sorokin S. P., Brain J. D. Pathways of clearance in mouse lungs exposed to iron oxide aerosols. Anat Rec. 1975 Mar;181(3):581–625. doi: 10.1002/ar.1091810304. [DOI] [PubMed] [Google Scholar]
  34. Turino G. M., Rodriguez J. R., Greenbaum L. M., Mandl I. Mechanisms of pulmonary injury. Am J Med. 1974 Sep;57(3):493–505. doi: 10.1016/0002-9343(74)90142-9. [DOI] [PubMed] [Google Scholar]
  35. Wahl L. M., Wahl S. M., Mergenhagen S. E., Martin G. R. Collagenase production by lymphokine-activated macrophages. Science. 1975 Jan 24;187(4173):261–263. doi: 10.1126/science.163038. [DOI] [PubMed] [Google Scholar]
  36. Watson A. Y., Brain J. D. Uptake of iron aerosols by mouse airway epithelium. Lab Invest. 1979 Apr;40(4):450–459. [PubMed] [Google Scholar]
  37. Weinbaum G., Marco V., Ikeda T., Mass B., Meranze D. R., Kimbel P. Enzymatic production of experimental emphysema in the dog. Route of exposure. Am Rev Respir Dis. 1974 Mar;109(3):351–357. doi: 10.1164/arrd.1974.109.3.351. [DOI] [PubMed] [Google Scholar]
  38. Werb Z., Gordon S. Elastase secretion by stimulated macrophages. Characterization and regulation. J Exp Med. 1975 Aug 1;142(2):361–377. doi: 10.1084/jem.142.2.361. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. White R., Lin H. S., Kuhn C., 3rd Elastase secretion by peritoneal exudative and alveolar macrophages. J Exp Med. 1977 Sep 1;146(3):802–808. doi: 10.1084/jem.146.3.802. [DOI] [PMC free article] [PubMed] [Google Scholar]

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