C5a initiates the inflammatory cascade in immune complex peritonitis
C5a initiates the inflammatory cascade in immune complex peritonitis
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DOI：
10.4049/jimmunol.173.5.3437
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发表时间：
2004-09-01
影响因子：
4.4
通讯作者：
Köhl, J
中科院分区：
文献类型：
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作者：
Godau, J;Heller, T;Köhl, J
免疫复合体(IC)诱导的炎症是几种自身免疫性疾病发病机制中不可或缺的一部分。ICS激活补体系统并与Ig G FcGammaR相互作用。在这项研究中，我们证明补体系统的激活，特别是C5a的产生，启动了IC腹膜炎的中性粒细胞炎症。我们发现，C5a受体信号的消融可以消除野生型小鼠的中性粒细胞募集，并阻止在FegammaRIIB(-/-)小鼠中看到的中性粒细胞迁移的增强，这表明C5aR信号是FcGammaR信号上游的关键初始事件。我们还提供了证据，证明C5a通过C5aR介导的对浸润性和驻留性腹膜细胞的效应功能直接启动炎症级联反应，并间接地通过改变驻留细胞上激活和抑制FcGammaR之间的平衡来向炎症表型转变。我们得出结论，补体激活和C5a的产生是IC诱导炎症的先决条件，它通过激活FcGammaR在自身免疫中放大补体诱导的炎症。
Immune complex (IC)-induced inflammation is integral to the pathogenesis of several autoimmune diseases. ICs activate the complement system and interact with IgG FcgammaR. In this study, we demonstrate that activation of the complement system, specifically generation of C5a, initiates the neutrophilic inflammation in IC peritonitis. We show that ablation of C5a receptor signaling abrogates neutrophil recruitment in wild-type mice and prevents the enhancement of neutrophil migration seen in FegammaRIIB(-/-) mice, suggesting that C5aR signaling is the crucial initial event upstream of FcgammaR signaling. We also provide evidence that C5a initiates the inflammatory cascade both directly, through C5aR-mediated effector functions on infiltrating and resident peritoneal cells, and indirectly, through shifting the balance between activating and inhibitory FcgammaRs on resident cells toward an inflammatory phenotype. We conclude that complement activation and C5a generation are prerequisites for IC-induced inflammation through activating FcgammaR, which amplifies complement-induced inflammation in autoimmunity.