Mediation of IgA induced lung injury in the rat. Role of macrophages and reactive oxygen products.
Acute lung injury in the rat has been induced by the instillation of affinity-purified mouse monoclonal IgA antibody with specific reactivity to the hapten dinitrophenol coupled to albumin. As previously reported, this model of lung injury requires an intact complement system but is independent of neutrophils. In contrast to macrophages obtained by bronchoalveolar lavage from rats receiving IgA into the airways in the absence of intravenously injected antigen, macrophages obtained from the lungs of rats developing IgA immune complex-induced lung injury were significantly increased in number, showed greater spontaneous generation of O2.-, and demonstrated significantly enhanced O2.- responses in the presence of an added stimulus, phorbol ester. Inhibition studies in vivo suggested that the IgA-induced lung injury is mediated by oxygen radicals generated from lung macrophages. Pretreatment of animals with superoxide dismutase, catalase, the iron chelator, deferoxamine, or the hydroxyl radical scavenger, dimethyl sulfoxide, suppressed the development of lung injury. Morphologically the lungs of protected animals showed increased numbers of mononuclear cells within the alveolar compartment but little evidence of alveolar or capillary injury, in contrast to unprotected animals in which there was evidence of severe injury, both to microvascular interstitial endothelial cells as well as to alveolar lining epithelial cells. These studies suggest that acute lung injury in the rat induced by IgA immune complexes is mediated by oxygen radical formation and that the macrophage may be the principle effector cell, as compared to IgG immune complex induced lung injury, which is also oxygen radical mediated but in which the neutrophil is the effector cell.
D000818:Animals; D002374:Catalase / Q000494:pharmacology; D003676:Deferoxamine / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004140:Dinitrophenols / Q000276:immunology; D005609:Free Radicals; D006241:Haptens / Q000276:immunology; D007105:Immune Complex Diseases / Q000276:immunology* / Q000378:metabolism; D007070:Immunoglobulin A / Q000276:immunology*; D008168:Lung / Q000473:pathology; D008171:Lung Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000473:pathology; D051381:Rats; D012710:Serum Albumin, Bovine / Q000276:immunology; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*
D004140:Dinitrophenols; D005609:Free Radicals; D006241:Haptens; D007070:Immunoglobulin A; D013481:Superoxides; D012710:Serum Albumin, Bovine; D002374:Catalase; D013482:Superoxide Dismutase; D003676:Deferoxamine; D004121:Dimethyl Sulfoxide