Johnson K J, Ward P A, Kunkel R G, Wilson B S
Lab Invest. 1986 May;54(5):499-506.
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.
通过向大鼠气道内滴注对与白蛋白偶联的半抗原二硝基苯酚具有特异性反应性的亲和纯化小鼠单克隆IgA抗体，可诱导大鼠发生急性肺损伤。如先前报道，这种肺损伤模型需要完整的补体系统，但与中性粒细胞无关。与在未静脉注射抗原的情况下接受IgA的大鼠经支气管肺泡灌洗获得的巨噬细胞相比，从发生IgA免疫复合物诱导的肺损伤的大鼠肺中获得的巨噬细胞数量显著增加，显示出更大的O2.-自发产生量，并且在添加佛波酯刺激物时表现出显著增强的O2.-反应。体内抑制研究表明，IgA诱导的肺损伤是由肺巨噬细胞产生的氧自由基介导的。用超氧化物歧化酶、过氧化氢酶、铁螯合剂去铁胺或羟基自由基清除剂二甲基亚砜对动物进行预处理可抑制肺损伤的发展。形态学上，与未受保护的动物相比，受保护动物的肺在肺泡腔内单核细胞数量增加，但几乎没有肺泡或毛细血管损伤的证据，未受保护的动物存在微血管间质内皮细胞以及肺泡内衬上皮细胞严重损伤的证据。这些研究表明，IgA免疫复合物诱导的大鼠急性肺损伤是由氧自由基形成介导的，与IgG免疫复合物诱导的肺损伤相比，巨噬细胞可能是主要效应细胞，IgG免疫复合物诱导的肺损伤也是由氧自由基介导的，但其中中性粒细胞是效应细胞。
