Fujii Takayuki, Hamano Yuki, Ueda Shiro, Akikusa Bunshiro, Yamasaki Sho, Ogawa Makoto, Saisho Hiromitsu, Verbeek J Sjef, Taki Shinsuke, Saito Takashi
Department of Molecular Genetics, Graduate School of Medicine, Chiba University, Chiba, Japan.
Kidney Int. 2003 Oct;64(4):1406-16. doi: 10.1046/j.1523-1755.2003.00203.x.
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.
Accelerated anti-GBM glomerulonephritis was induced in FcgammaRI-/-, FcgammaRIII-/-, and FcRgamma-/- mice by preimmunization with rabbit IgG followed by inoculation of rabbit anti-GBM antibody. Histologic analysis and immunostaining of renal sections were performed.
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.
Accelerated nephrotoxic glomerulonephritis is induced predominantly through FcgammaRIII but not FcgammaRI.
肾毒性肾小球肾炎是通过给予抗肾小球基底膜（GBM）抗体诱导产生的。我们之前利用FcRγ缺陷（-/-）小鼠证明，免疫球蛋白G（IgG）的Fc受体（FcγR）在加速性肾毒性肾小球肾炎的诱导过程中起关键作用。由于FcRγ-/-小鼠缺乏两种激活型FcγR，即FcγRI和FcγRIII的细胞表面表达。本研究旨在确定负责诱导肾毒性肾小球肾炎的FcγR。
通过用兔IgG进行预免疫，然后接种兔抗GBM抗体，在FcγRI-/-、FcγRIII-/-和FcRγ-/-小鼠中诱导加速性抗GBM肾小球肾炎。对肾切片进行组织学分析和免疫染色。
给予抗GBM抗体后，FcγRI-/-小鼠以及野生型小鼠均出现伴有高氮血症的严重肾小球肾炎。相比之下，FcγRIII-/-小鼠的肾脏受累程度要轻得多，类似于FcRγ-/-小鼠。组织学上，FcγRI-/-小鼠表现为毛细血管内增生、肾小球血栓形成和新月体形成，而FcγRIII-/-小鼠仅表现为肾小球细胞增多。通过免疫染色在所有三种FcR-/-小鼠类型中均同等观察到抗GBM抗体、自身抗体和补体C3沿GBM的沉积。
加速性肾毒性肾小球肾炎主要通过FcγRIII而非FcγRI诱导产生。
