Warren J S, Barton P A, Jones M L
Department of Pathology, University of Michigan, Medical School, Ann Arbor 48109-0602.
Am J Pathol. 1991 Mar;138(3):581-90.
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.
近期研究表明，急性γG免疫球蛋白（IgG）免疫复合物肺损伤的发生部分依赖于肿瘤坏死因子（TNF）介导的中性粒细胞（PMN）募集机制。作者试图进一步明确肺内TNF在IgG肺泡炎中的作用，并研究其在IgA免疫复合物肺泡炎（一种与中性粒细胞无关的急性肺损伤模型）中的作用。IgG免疫复合物肺损伤导致肺内TNF活性显著升高，同时伴有肺内PMN逐渐积聚。气管内滴注中和浓度的抗TNF抗体可显著降低4小时时测得的PMN流入量，但对2小时时定量的PMN募集无影响。IgA免疫复合物沉积导致急性肺损伤，伴有肺内单核吞噬细胞数量增加，但中性粒细胞很少。从IgA免疫复合物损伤大鼠获得的肺灌洗液中同时含有中性粒细胞和单核细胞趋化活性，尽管其浓度比IgG介导的肺泡炎中观察到的低两到四倍。与IgG复合物介导的肺泡炎不同，IgA损伤大鼠的肺灌洗液中没有TNF活性。气管内给予抗TNF抗体对IgA肺损伤的发展没有影响，这通过形态学和血管通透性测量来评估。体外将分离的肺泡巨噬细胞暴露于已形成的IgG免疫复合物中会导致剂量依赖性的TNF分泌，而暴露于IgA复合物中则导致TNF分泌水平非常低。这些数据表明，TNF介导的肺中性粒细胞募集（在IgG肺损伤中）主要表现在肺泡炎发展的后期（约4小时）。在进展性IgA免疫复合物肺泡炎中肺内几乎没有TNF活性，这可能部分解释了该模型中观察到的有限的PMN募集。
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