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

Kidney Int. 1998 Oct;54(4):1166-74. doi: 10.1046/j.1523-1755.1998.00108.x.


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 gamma chain [gamma(-/-)] or Fc gammaRIIB [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 gamma(-/-) mice.

Results: In gamma(-/-) 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 gamma(-/-) 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 alpha smooth muscle actin in the mesangial cells and interstitium. Those injuries in gamma(-/-) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Angiotensin II / metabolism*
  • Angiotensin Receptor Antagonists
  • Animals
  • Basement Membrane / immunology
  • Basement Membrane / injuries
  • Basement Membrane / pathology
  • Benzimidazoles / pharmacology
  • Biphenyl Compounds / pharmacology
  • Disease Models, Animal
  • Female
  • Glomerulonephritis / etiology*
  • Glomerulonephritis / pathology
  • Glomerulonephritis / physiopathology*
  • Kidney Glomerulus / immunology
  • Kidney Glomerulus / injuries
  • Kidney Glomerulus / pathology
  • Macrophages / pathology
  • Male
  • Mice
  • Mice, Knockout
  • Monocytes / pathology
  • Proteinuria / etiology
  • Receptor, Angiotensin, Type 1
  • Receptor, Angiotensin, Type 2
  • Receptors, IgG / metabolism*
  • Tetrazoles*


  • Actins
  • Angiotensin Receptor Antagonists
  • Benzimidazoles
  • Biphenyl Compounds
  • Receptor, Angiotensin, Type 1
  • Receptor, Angiotensin, Type 2
  • Receptors, IgG
  • Tetrazoles
  • Angiotensin II
  • candesartan cilexetil