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. 1991 Mar;138(3):581–590.

Contrasting roles for tumor necrosis factor in the pathogeneses of IgA and IgG immune complex lung injury.

J S Warren 1, P A Barton 1, M L Jones 1
PMCID: PMC1886288  PMID: 2000937

Abstract

Recent studies suggest that development of acute gamma G immunoglobulin (IgG) immune complex lung injury is partially dependent on a tumor necrosis factor (TNF)-dependent mechanisms of neutrophil (PMN) recruitment. The authors have sought to further define the role of intrapulmonary TNF in IgG alveolitis and to examine its role in IgA immune complex alveolitis, a neutrophil-independent model of acute lung injury. IgG immune complex lung injury resulted in a marked rise in intrapulmonary TNF activity accompanied by progressive pulmonary PMN accumulation. Intratracheal instillation of neutralizing concentrations of anti-TNF markedly reduced PMN influx measured at 4 hours but had no effect on PMN recruitment quantitated at 2 hours. IgA immune complex deposition resulted in acute lung injury accompanied by increased numbers of intrapulmonary mononuclear phagocytes but few neutrophils. Lung lavage fluids obtained from IgA immune complex-injured rats contained both neutrophil and monocyte chemotactic activities, albeit at twofold to fourfold lower concentrations than observed in IgG-mediated alveolitis. In contrast to IgG complex-mediated alveolitis, lung lavage fluids from IgA-injured rats contained no TNF activity. Intratracheal administration of anti-TNF antibodies had no effect on the development of IgA lung injury as assessed by morphology and measurements of vascular permeability. In vitro exposure of isolated alveolar macrophages to performed IgG immune complexes resulted in dose-dependent TNF secretion, while exposure to IgA complexes resulted in very low levels of TNF secretion. These data suggest that TNF-mediated pulmonary neutrophil recruitment (in IgG lung injury) is manifest chiefly in the late phase (approximately 4 hours) of developing alveolitis. The virtual absence of intrapulmonary TNF activity in evolving IgA immune complex alveolitis may in part account for the limited PMN recruitment observed in this model.

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