Distinct contribution of Fc receptors and angiotensin II-dependent pathways in anti-GBM glomerulonephritis

Yusuke Suzuki, Isao Shirato, Ko Okumura, Jeffrey V. Ravetch, Toshiyuki Takai, Yasuhiko Tomino, Chisei Ra

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147 Citations (Scopus)


Background. The contribution of antibody and/or immune-complex to the pathogenesis of immunologically-mediated glomerulonephritis is not fully understood, although it has been recently clarified that Fc receptors (FcRs) play critical roles in the inflammatory cascade. We therefore re-evaluated the classical model of glomerulonephritis, anti-glomerular basement membrane antibody-induced glomerulonephritis (Anti-GBM GN), from the standpoint of FcRs and also investigated the residual FcR-independent mechanisms. Methods. We adopted an Anti-GBM GN mouse model that has two strains deficient in the FcR γ chain [γ(-/-)] or FcγRIIB [RII(-/-)], and analyzed functional (urinary protein, serum creatinine, BUN) and pathological changes of the glomeruli. For the analyses of FcR-independent mechanisms, several doses of nephrotoxic serum were applied, and then mice were treated either with cobra venom factor or an angiotensin II type 1 receptor antagonist in γ(-/-) mice. Results. In γ(-/-) mice, renal injuries were dramatically attenuated with an absence of polymorphonuclear cell (PMN) influx, while RII(-/-) mice suffered accelerated glomerular injuries in spite of a normal PMN influx. In the absence of FcR-dependent effects in γ(-/-) mice, the FcR-independent pathway lead to chronic renal damage characterized by mesangial proliferation and progressive expansion of mesangial area, with monocyte/macrophage accumulation and with the expression of α smooth muscle actin in the mesangial cells and interstitium. Those injuries in γ(-/-) mice were not attenuated by the decomplementation, but completely abolished by using an angiotensin II type 1 receptor antagonist. Conclusions. Our results clearly demonstrate that FcRs play a pivotal role in Anti-GBM GN, especially in its acute phase. We further clarified the existence of FcR and complement- independent but antibody-dependent pathway. Furthermore, we found that those pathological changes were strongly related to the renin-angiotensin system.

Original languageEnglish
Pages (from-to)1166-1174
Number of pages9
JournalKidney International
Issue number4
Publication statusPublished - 1998


  • Angiotensin II
  • Anti-GBM antibody-induced glomerulonephritis
  • FcR γ chain
  • FcγRIIB
  • Immune complex
  • Monocyte/macrophage
  • Polymorphonuclear cell


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