Abolition of anti-glomerular basement membrane antibody-mediated glomerulonephritis in FcRγ-deficient mice

Hisashi Wakayama, Yoshinori Hasegawa, Tsutomu Kawabe, Toru Hara, Seiichi Matsuo, Masashi Mizuno, Toshiyuki Takai, Hitoshi Kikutani, Kaoru Shimokata

Research output: Contribution to journalArticlepeer-review

44 Citations (Scopus)

Abstract

Several recent studies have demonstrated the central role of Fc receptors (FcR) rather than the complement system in triggering hypersensitivity reactions. We investigated the role of FcR for IgG (FcγR) using a murine model of accelerated anti-glomerular basement membrane (GBM) antibody-mediated glomerulonephritis as a representative of type II hypersensitivity diseases. Intravenous injection of rabbit anti-GBM antibody after preimmunization with normal rabbit IgG induced proteinuria and azotemia in wild-type C57BL/6 and CD40(+/-) mice but not in FcR γ chain (FcRγ)(-/-) mice or CD40(-/-) mice. Light microscopic findings revealed marked tissue damage in the glomeruli of wild-type C57BL/6 and CD40(+/-) mice. However, no tissue damage except polymorphonuclear cell infiltration was observed in the glomeruli of FcRγ(-/-) mice. The glomeruli of CD40(-/-) mice were almost normal. Immunohistochemistry revealed the binding of rabbit IgG to the GBM in all mice injected with anti-GBM antibody. However, depositions of mouse IgG and complement to the glomeruli were not observed in CD40(-/-) mice, and deposition of fibrin was not observed in FcRγ(-/-) or CD40(-/-) mice. These findings suggest that FcγR may initiate anti-GBM antibody-mediated renal disease. We conclude that FcγR rather than the complement system is critically involved in the development of type II hypersensitivity diseases.

Original languageEnglish
Pages (from-to)1182-1190
Number of pages9
JournalEuropean Journal of Immunology
Volume30
Issue number4
DOIs
Publication statusPublished - 2000

Keywords

  • Fc receptor
  • Glomerulonephritis
  • IgG
  • Polymorphonuclear cell
  • Type II hypersensitivity

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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