In vitro activation of rat neutrophils and alveolar macrophages with IgA and IgG immune complexes. Implications for immune complex-induced lung injury.
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.
Warren
J S
JS
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602.
Kunkel
S L
SL
Johnson
K J
KJ
Ward
P A
PA
D000818:Animals; D000936:Antigen-Antibody Complex / Q000502:physiology*; D003182:Complement C5 / Q000502:physiology; D015936:Complement C5a; D005609:Free Radicals; D007070:Immunoglobulin A / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D008171:Lung Diseases / Q000276:immunology*; D008247:Lysosomes / Q000201:enzymology; D008264:Macrophages / Q000378:metabolism / Q000502:physiology*; D008297:Male; D009504:Neutrophils / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D010100:Oxygen / Q000096:biosynthesis; D010587:Phagocytosis; D011650:Pulmonary Alveoli / Q000166:cytology*; D051381:Rats; D011919:Rats, Inbred Strains; D013481:Superoxides / Q000096:biosynthesis
D000936:Antigen-Antibody Complex; D003182:Complement C5; D005609:Free Radicals; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D013481:Superoxides; D015936:Complement C5a; D010100:Oxygen