[HTML][HTML] Distinct contribution of Fc receptors and angiotensin II-dependent pathways in anti-GBM glomerulonephritis
Y Suzuki, I Shirato, K Okumura, JV Ravetch, T Takai… - Kidney international, 1998 - Elsevier
Y Suzuki, I Shirato, K Okumura, JV Ravetch, T Takai, Y Tomino, C Ra
Kidney international, 1998•ElsevierDistinct contribution of Fc receptors and angiotensin II-dependent pathways in anti-GBM
glomerulonephritis. 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) …
glomerulonephritis. 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) …
Distinct contribution of Fc receptors and angiotensin II-dependent pathways in anti-GBM glomerulonephritis.
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.
Elsevier