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The American Journal of Pathology logoLink to The American Journal of Pathology
. 1987 Dec;129(3):578–588.

In vitro activation of rat neutrophils and alveolar macrophages with IgA and IgG immune complexes. Implications for immune complex-induced lung injury.

J S Warren 1, S L Kunkel 1, K J Johnson 1, P A Ward 1
PMCID: PMC1899828  PMID: 2827492

Abstract

In the rat, both IgG and IgA immune complexes induce oxygen radical mediated lung injury that is partially complement-dependent. In vivo studies have suggested that the chief sources of oxygen radicals in IgG and IgA immune complex-induced lung injury are neutrophils and tissue macrophages, respectively. The current studies have been designed to provide additional insights into these two models of tissue injury. Preformed monoclonal IgG and IgA immune complexes stimulated dose-dependent O2-. and H2O2 production by alveolar macrophages. In contrast, neutrophils exhibited O2-. production and lysosomal enzyme secretion in response to IgG immune complexes, but not in response to IgA complexes. There is evidence that C5a significantly amplifies these responses. Purified human C5a enhanced the O2-. responses of neutrophils activated with IgG immune complexes and alveolar macrophages activated with either IgG or IgA immune complexes. Addition of C5a alone to neutrophils or alveolar macrophages had no direct stimulatory effect as measured by O2-. production. The observation that O2-. responses of immune complex-activated alveolar macrophages can be significantly enhanced by the presence of C5a and that C5a can also enhance O-2. responses of IgG immune complex-stimulated neutrophils suggests a potential amplification mechanism through which complement may participate in both IgG and IgA immune complex-induced lung injury. The present data corroborate in vivo studies which suggest that IgG immune complex lung injury is primarily neutrophil-mediated, whereas IgA complex lung injury is predominantly macrophage-mediated.

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Selected References

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

  1. Babior B. M., Kipnes R. S., Curnutte J. T. Biological defense mechanisms. The production by leukocytes of superoxide, a potential bactericidal agent. J Clin Invest. 1973 Mar;52(3):741–744. doi: 10.1172/JCI107236. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bender J. G., McPhail L. C., Van Epps D. E. Exposure of human neutrophils to chemotactic factors potentiates activation of the respiratory burst enzyme. J Immunol. 1983 May;130(5):2316–2323. [PubMed] [Google Scholar]
  3. Beswick P. H., Kay A. B. The effects of an ECF-A and formyl methionyl chemotactic peptides on oxidative metabolism of human eosinophils and neutrophils. Clin Exp Immunol. 1981 Feb;43(2):399–407. [PMC free article] [PubMed] [Google Scholar]
  4. Brentjens J. R., O'Connell D. W., Pawlowski I. B., Hsu K. C., Andres G. A. Experimental immune complex disease of the lung. The pathogenesis of a laboratory model resembling certain human interstitial lung diseases. J Exp Med. 1974 Jul 1;140(1):105–125. doi: 10.1084/jem.140.1.105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Carter S. B. Effects of cytochalasins on mammalian cells. Nature. 1967 Jan 21;213(5073):261–264. doi: 10.1038/213261a0. [DOI] [PubMed] [Google Scholar]
  6. Couser W. G., Salant D. J. In situ immune complex formation and glomerular injury. Kidney Int. 1980 Jan;17(1):1–13. doi: 10.1038/ki.1980.1. [DOI] [PubMed] [Google Scholar]
  7. Drath D. B., Karnovsky M. L. Superoxide production by phagocytic leukocytes. J Exp Med. 1975 Jan 1;141(1):257–262. doi: 10.1084/jem.141.1.257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. English D., Roloff J. S., Lukens J. N. Chemotactic factor enhancement of superoxide release from fluoride and phorbol myristate acetate stimulated neutrophils. Blood. 1981 Jul;58(1):129–134. [PubMed] [Google Scholar]
  9. Fantone J., Senior R. M., Kreutzer D. L., Jones M., Ward P. A. Biochemical quantitation of the chemotactic factor inactivator activity in human serum. J Lab Clin Med. 1979 Jan;93(1):17–24. [PubMed] [Google Scholar]
  10. Gauldie J., Richards C., Lamontagne L. Fc receptors for IgA and other immunoglobulins on resident and activated alveolar macrophages. Mol Immunol. 1983 Sep;20(9):1029–1037. doi: 10.1016/0161-5890(83)90044-5. [DOI] [PubMed] [Google Scholar]
  11. Gerard C., Hugli T. E. Anaphylatoxin from the fifth component of porcine complement. Purification and partial chemical characterization. J Biol Chem. 1979 Jul 25;254(14):6346–6351. [PubMed] [Google Scholar]
  12. Goldstein I. M., Roos D., Kaplan H. B., Weissmann G. Complement and immunoglobulins stimulate superoxide production by human leukocytes independently of phagocytosis. J Clin Invest. 1975 Nov;56(5):1155–1163. doi: 10.1172/JCI108191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Henson P. M., Oades Z. G. Stimulation of human neutrophils by soluble and insoluble immunoglobulin aggregates. Secretion of granule constituents and increased oxidation of glucose. J Clin Invest. 1975 Oct;56(4):1053–1061. doi: 10.1172/JCI108152. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Henson P. M., Zanolari B., Schwartzman N. A., Hong S. R. Intracellular control of human neutrophil secretion. I. C5a-induced stimulus-specific desensitization and the effects of cytochalasin B. J Immunol. 1978 Sep;121(3):851–855. [PubMed] [Google Scholar]
  15. Hugli T. E., Gerard C., Kawahara M., Scheetz M. E., 2nd, Barton R., Briggs S., Koppel G., Russell S. Isolation of three separate anaphylatoxins from complement-activated human serum. Mol Cell Biochem. 1981 Dec 4;41:59–66. doi: 10.1007/BF00225297. [DOI] [PubMed] [Google Scholar]
  16. Issekutz A. C., Lee K. Y., Biggar W. D. Enhancement of human neutrophil bactericidal activity by chemotactic factors. Infect Immun. 1979 May;24(2):295–301. doi: 10.1128/iai.24.2.295-301.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Johnson K. J., Ward P. A. Acute immunologic pulmonary alveolitis. J Clin Invest. 1974 Aug;54(2):349–357. doi: 10.1172/JCI107770. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Johnson K. J., Ward P. A., Kunkel R. G., Wilson B. S. Mediation of IgA induced lung injury in the rat. Role of macrophages and reactive oxygen products. Lab Invest. 1986 May;54(5):499–506. [PubMed] [Google Scholar]
  19. Johnson K. J., Ward P. A. Role of oxygen metabolites in immune complex injury of lung. J Immunol. 1981 Jun;126(6):2365–2369. [PubMed] [Google Scholar]
  20. Johnson K. J., Wilson B. S., Till G. O., Ward P. A. Acute lung injury in rat caused by immunoglobulin A immune complexes. J Clin Invest. 1984 Aug;74(2):358–369. doi: 10.1172/JCI111431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kaplan R. L., Schocket A. L., King T. E., Maulitz R. M., Good J. T., Jr, Stanford R. E., Sahn S. A. A model of immune complex-mediated pleuropulmonary injury; evidence of deposition of circulating immune complexes in the lung. Am J Pathol. 1980 Jul;100(1):115–130. [PMC free article] [PubMed] [Google Scholar]
  22. Kaysen G. A., Myers B. D., Couser W. G., Rabkin R., Felts J. M. Mechanisms and consequences of proteinuria. Lab Invest. 1986 May;54(5):479–498. [PubMed] [Google Scholar]
  23. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  24. Lehmeyer J. E., Snyderman R., Johnston R. B., Jr Stimulation of neutrophil oxidative metabolism by chemotactic peptides: influence of calcium ion concentration and cytochalasin B and comparison with stimulation by phorbol myristate acetate. Blood. 1979 Jul;54(1):35–45. [PubMed] [Google Scholar]
  25. Manderino G. L., Suarez A. F., Kunkel S. L., Ward P. A., Hirata A. A., Showell H. Purification of human C5a des arg by immunoadsorbent and molecular sieve chromatography. J Immunol Methods. 1982 Aug 27;53(1):41–50. doi: 10.1016/0022-1759(82)90238-1. [DOI] [PubMed] [Google Scholar]
  26. Pfaffenbach G., Lamm M. E., Gigli I. Activation of the guinea pig alternative complement pathway by mouse IgA immune complexes. J Exp Med. 1982 Jan 1;155(1):231–247. doi: 10.1084/jem.155.1.231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Sanger J. W., Holtzer H. Cytochalasin B: effects on cell morphology, cell adhesion, and mucopolysaccharide synthesis (cultured cells-contractile microfilaments-glycoproteins-embryonic cells-sorting-out). Proc Natl Acad Sci U S A. 1972 Jan;69(1):253–257. doi: 10.1073/pnas.69.1.253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Scherzer H., Ward P. A. Lung injury produced by immune complexes of varying composition. J Immunol. 1978 Sep;121(3):947–952. [PubMed] [Google Scholar]
  29. Smith R. J., Iden S. S. Phorbol myristate acetate-induced release of granule enzymes from human neutrophils: inhibition by the calcium antagonist, 8-(N,N-diethylamino)-octyl 3,4,5-trimethoxybenzoate hydrochloride. Biochem Biophys Res Commun. 1979 Nov 14;91(1):263–271. doi: 10.1016/0006-291x(79)90612-0. [DOI] [PubMed] [Google Scholar]
  30. Stossel T. P., Hartwig J. H. Interactions of actin, myosin, and a new actin-binding protein of rabbit pulmonary macrophages. II. Role in cytoplasmic movement and phagocytosis. J Cell Biol. 1976 Mar;68(3):602–619. doi: 10.1083/jcb.68.3.602. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Stubbs M., Kühner A. V., Glass E. A., David J. R., Karnovsky M. L. Metabolic and functonal studies on activated mouse macrophages. J Exp Med. 1973 Feb 1;137(2):537–542. doi: 10.1084/jem.137.2.537. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Thurman R. G., Ley H. G., Scholz R. Hepatic microsomal ethanol oxidation. Hydrogen peroxide formation and the role of catalase. Eur J Biochem. 1972 Feb;25(3):420–430. doi: 10.1111/j.1432-1033.1972.tb01711.x. [DOI] [PubMed] [Google Scholar]
  33. Van Epps D. E., Garcia M. L. Enhancement of neutrophils function as a result of prior exposure to chemotactic factor. J Clin Invest. 1980 Aug;66(2):167–175. doi: 10.1172/JCI109841. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Ward P. A., Duque R. E., Sulavik M. C., Johnson K. J. In vitro and in vivo stimulation of rat neutrophils and alveolar macrophages by immune complexes. Production of O-2 and H2O2. Am J Pathol. 1983 Mar;110(3):297–309. [PMC free article] [PubMed] [Google Scholar]
  35. Ward P. A., Sulavik M. C., Johnson K. J. Rat neutrophil activation and effects of lipoxygenase and cyclooxygenase inhibitors. Am J Pathol. 1984 Aug;116(2):223–233. [PMC free article] [PubMed] [Google Scholar]
  36. Weiss S. J., Ward P. A. Immune complex induced generation of oxygen metabolites by human neutrophils. J Immunol. 1982 Jul;129(1):309–313. [PubMed] [Google Scholar]
  37. Yost F. J., Jr, Fridovich I. Superoxide radicals and phagocytosis. Arch Biochem Biophys. 1974 Apr 2;161(2):395–401. doi: 10.1016/0003-9861(74)90320-8. [DOI] [PubMed] [Google Scholar]
  38. Zigmond S. H., Hirsch J. G. Effects of cytochalasin B on polymorphonuclear leucocyte locomotion, phagocytosis and glycolysis. Exp Cell Res. 1972 Aug;73(2):383–393. doi: 10.1016/0014-4827(72)90062-6. [DOI] [PubMed] [Google Scholar]
  39. Zurier R. B., Hoffstein S., Weissmann G. Cytochalasin B: effect on lysosomal enzyme release from human leukocytes. Proc Natl Acad Sci U S A. 1973 Mar;70(3):844–848. doi: 10.1073/pnas.70.3.844. [DOI] [PMC free article] [PubMed] [Google Scholar]

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