Impaired inflammatory responses in the reverse arthus reaction through genetic deletion of the C5a receptor
Impaired inflammatory responses in the reverse arthus reaction through genetic deletion of the C5a receptor
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DOI：
10.1084/jem.186.5.749
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发表时间：
1997-08-29
影响因子：
15.3
通讯作者：
Gerard, C
中科院分区：
文献类型：
--
作者：
Hopken, UE;Lu, B;Gerard, C
我们最近证实，基因靶向破坏C5 a过敏毒素受体可预防免疫复合物介导的炎症中的肺损伤。在这项研究中，我们比较了C5 aR缺乏在免疫复合物诱导的腹腔和皮肤炎症中的作用与我们的免疫复合物肺泡炎模型的结果。与野生型同窝出生小鼠相比，C5 aR缺陷小鼠在腹膜反向被动Arthus反应中表现出中性粒细胞迁移减少以及TNF-α和白细胞介素6水平降低。在皮肤中的反向被动Arthus反应中，中性粒细胞流入和水肿形成的充分表达也需要C5 aR; C5 aR缺陷小鼠表现出中性粒细胞迁移减少和微血管通透性变化。与我们在免疫复合物诱导的肺部炎症中的研究相反，C5 aR缺乏不能完全防止腹膜腔和皮肤的损伤。这些数据表明C5 aR及其配体在肺中的反向被动Arthus反应中起主导作用，并且与免疫复合物介导的腹膜炎和皮肤损伤中的其他炎症介质一起起协同作用。
We recently demonstrated that gene-targeted disruption of the C5a anaphylatoxin receptor prevented lung injury in immune complex-mediated inflammation. In this study, we compare the effect of C5aR deficiency in immune complex-induced inflammation in the peritoneal cavity and skin with the results derived from our immune complex alveolitis model. C5aR-deficient mice exhibit decreased migration of neutrophils and decreased levels of TNF-alpha and interleukin 6 in the peritoneal reverse passive Arthus reaction compared to their wild-type littermates. In the reverse passive Arthus reaction in the skin the C5aR was also required for the full expression of neutrophil influx and edema formation; C5aR-deficient mice showed reduced neutrophil migration and microvascular permeability changes. In contrast to our studies in immune complex-induced lung inflammation, C5aR deficiency does not completely prevent injury in the peritoneal cavity and skin. These data indicate a dominant role for the C5aR and its ligand in the reverse passive Arthus reaction in the lung and a synergistic role together with other inflammatory mediators in immune complex-mediated peritonitis and skin injury.