Predominant role of FcγRIII in the induction of accelerated nephrotoxic glomerulonephritis

Takayuki Fujii, Yuki Hamano, Shiro Ueda, Bunshiro Akikusa, Sho Yamasaki, Makoto Ogawa, Hiromitsu Saisho, J. Sjef Verbeek, Shinsuke Taki, Takashi Saito

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    Abstract

    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) (FcγR) play crucial roles in the induction of accelerated nephrotoxic glomerulonephritis by using FcRγ-deficient (-/-) mice. Since FcRγ-/- mice lack the cell surface expression of two activating FcγRs, FcγRI and FcγRIII. The present study aims to identify the FcγR responsible for the induction of nephrotoxic glomerulonephritis. Methods. Accelerated anti-GBM glomerulonephritis was induced in FcγRI-/-, FcγRIII-/-, and FcRγ-/- mice by preimmunization with rabbit IgG followed by inoculation of rabbit anti-GBM antibody. Histologic analysis and immunostaining of renal sections were performed. Results. FcγRI-/- mice as well as wild-type mice showed severe glomerulonephritis with hypernitremia by the administration of anti-GBM antibody. In contrast, FcγRIII-/- mice showed much milder renal involvement, similar to FcRγ-/-mice. Histologically, FcγRI-/- mice showed intracapillary proliferation, glomerular thrombosis, and crescent formation, whereas FcγRIII-/- 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 FcγRIII but not FcγRI.

    Original languageEnglish
    Pages (from-to)1406-1416
    Number of pages11
    JournalKidney International
    Volume64
    Issue number4
    DOIs
    Publication statusPublished - Oct 1 2003

    All Science Journal Classification (ASJC) codes

    • Nephrology

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    Fujii, T., Hamano, Y., Ueda, S., Akikusa, B., Yamasaki, S., Ogawa, M., Saisho, H., Verbeek, J. S., Taki, S., & Saito, T. (2003). Predominant role of FcγRIII in the induction of accelerated nephrotoxic glomerulonephritis. Kidney International, 64(4), 1406-1416. https://doi.org/10.1046/j.1523-1755.2003.00203.x