Predominant role of FcγRIII in the induction of accelerated nephrotoxic glomerulonephritis
Predominant role of FcγRIII in the induction of accelerated nephrotoxic glomerulonephritis
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DOI：
10.1046/j.1523-1755.2003.00203.x
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发表时间：
2003-10-01
影响因子：
19.6
通讯作者：
Saito, T
中科院分区：
文献类型：
--
作者：
Fujii, T;Hamano, Y;Saito, T
背景。肾毒性肾小球肾炎是由抗肾小球基底膜（GBM）抗体引起的。我们之前已经证明免疫球蛋白G (IgG) （FcgammaR）的Fc受体在诱导加速肾毒性肾小球肾炎中发挥关键作用，通过使用fgamma缺陷（-/-）小鼠。由于FcRgamma-/-小鼠缺乏两种激活FcgammaRs， FcgammaRI和fcgammarii的细胞表面表达。本研究旨在鉴定诱导肾毒性肾小球肾炎的FcgammaR。采用兔IgG预免疫，再接种兔抗gbm抗体，诱导FcgammaRI-/-、fcgammarii -/-和FcRgamma-/-小鼠加速抗gbm肾小球肾炎。对肾切片进行组织学分析和免疫染色。fggammari -/-小鼠和野生型小鼠经抗gbm抗体处理后均表现为严重的肾小球肾炎伴高氮血症。相比之下，FcgammaRIII-/-小鼠的肾脏受累程度较轻，与FcRgamma-/-小鼠相似。组织学上，FcgammaRI-/-小鼠表现为毛细血管内增生、肾小球血栓形成和新月形成，而fcgammarii -/-小鼠仅表现为肾小球高细胞改变。免疫染色法观察到三种FcR-/-型小鼠沿GBM的抗GBM抗体、自体抗体和补体C3的沉积相同。加速肾毒性肾小球肾炎主要通过fcgammarii而不是FcgammaRI诱导。
Background. Nephrotoxic glomerulonephritis is induced by the administration of antibody against the glomerular basement membrane (GBM). We demonstrated previously that Fc receptors for immunoglobulin G (IgG) (FcgammaR) play crucial roles in the induction of accelerated nephrotoxic glomerulonephritis by using FcRgamma-deficient (-/-) mice. Since FcRgamma-/- mice lack the cell surface expression of two activating FcgammaRs, FcgammaRI and FcgammaRIII. The present study aims to identify the FcgammaR responsible for the induction of nephrotoxic glomerulonephritis.Methods. Accelerated anti-GBM glomerulonephritis was induced in FcgammaRI-/-, FcgammaRIII-/-, and FcRgamma-/- mice by pre-immunization with rabbit IgG followed by inoculation of rabbit anti-GBM antibody. Histologic analysis and immunostaining of renal sections were performed.Results. FcgammaRI-/- mice as well as wild-type mice showed severe glomerulonephritis with hypernitremia by the administration of anti-GBM antibody. In contrast, FcgammaRIII-/- mice showed much milder renal involvement, similar to FcRgamma-/- mice. Histologically, FcgammaRI-/- mice showed intracapillary proliferation, glomerular thrombosis, and crescent formation, whereas FcgammaRIII-/- mice showed only glomerular hypercellular changes. The depositions of anti-GBM antibodies, autologous antibodies and complement C3 along the GBM were equally observed among all three FcR-/- mouse types by immunostaining.Conclusions. Accelerated nephrotoxic glomerulonephritis is induced predominantly through FcgammaRIII but not FcgammaRI.