Park S Y, Ueda S, Ohno H, Hamano Y, Tanaka M, Shiratori T, Yamazaki T, Arase H, Arase N, Karasawa A, Sato S, Ledermann B, Kondo Y, Okumura K, Ra C, Saito T
Department of Molecular Genetics, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
J Clin Invest. 1998 Sep 15;102(6):1229-38. doi: 10.1172/JCI3256.
Immune complex-mediated inflammation is a common mechanism of various autoimmune diseases. Glomerulonephritis (GN) is one of these diseases, and the main mechanism of the induction of GN has been unclear. We examined the contribution of Fc receptors in the induction of nephrotoxic GN by establishing and analyzing mice deficient in the Fc receptor gamma chain (FcRgamma). Whereas all wild-type mice died from severe glomerulonephritis with hypernitremia by administration of anti-glomerular basement membrane (GBM) antibodies, all FcRgamma-deficient mice survived. Histologically, wild-type mice showed glomerular hypercellularity and thrombotic changes, whereas the renal tissue in FcRgamma-deficient mice was almost intact. Deposition of anti-GBM antibody as well as complement components in the GBM were equally observed in both wild-type and knockout mice. These results demonstrate that the triggering of this type of glomerulonephritis is completely dependent on FcR+ cells.
免疫复合物介导的炎症是多种自身免疫性疾病的常见机制。肾小球肾炎（GN）是其中一种疾病，而GN诱导的主要机制尚不清楚。我们通过建立和分析Fc受体γ链（FcRγ）缺陷小鼠，研究了Fc受体在肾毒性GN诱导中的作用。通过给予抗肾小球基底膜（GBM）抗体，所有野生型小鼠均死于伴有高钠血症的严重肾小球肾炎，而所有FcRγ缺陷小鼠均存活。组织学上，野生型小鼠表现出肾小球细胞增多和血栓形成变化，而FcRγ缺陷小鼠的肾组织几乎完好无损。在野生型和基因敲除小鼠中均同样观察到抗GBM抗体以及补体成分在GBM中的沉积。这些结果表明，这类肾小球肾炎的触发完全依赖于FcR+细胞。
