Nephrotoxic nephritis is mediated by Fcgamma receptors on circulating leukocytes and not intrinsic renal cells.
BACKGROUND
There is evidence that mesangial cells express Fcgamma receptors in vitro, but the in vivo relevance of this is not known. FcRgamma-/- mice lack the gamma chain signaling subunit and therefore do not express the activator Fcgamma receptors (FcgammaRI and FcgammaRIII) or the high affinity IgE receptor, FcepsilonRI. FcRgamma-/- mice were protected from renal inflammation following the induction of accelerated nephrotoxic nephritis using sheep anti-mouse glomerular basement membrane anti-serum in mice sensitized to sheep IgG.


METHODS
In order to test whether Fcgamma receptors had a role on intrinsic renal cells during nephritis, bone marrow cells were transplanted between wild-type (WT) mice and mice with a gene-targeted deletion of FcRgamma. Donor marrow reconstitution was confirmed by flow cytometric analysis of peripheral blood for FcgammaRIII, and the susceptibility of the transplanted mice to accelerated nephrotoxic nephritis was tested.


RESULTS
Following the induction of nephrotoxic nephritis, FcRgamma-/- mice transplanted with WT bone marrow developed as much renal disease as WT mice transplanted with WT bone marrow. In contrast, WT mice transplanted with FcRgamma-/- marrow were completely protected from glomerular crescents, thrombosis, albuminuria and renal impairment, as were FcRgamma-/- mice transplanted with FcRgamma-/- marrow. Mice with FcRgamma-/- marrow had prolonged survival, but by day 28 after nephrotoxic serum injection they had developed mesangial hypercellularity and a macrophage influx caused by non-FcRgamma dependent mechanisms.


CONCLUSIONS
Despite previous evidence that mesangial cells express Fcgamma receptors in vitro, they have no role in an FcRgamma-dependent model of glomerulonephritis in vivo.
Tarzi
Ruth M
RM
Division of Medicine and Department of Histopathology, Imperial College School of Medicine, Hammersmith Hospital, London, England.
Davies
Kevin A
KA
Robson
Michael G
MG
Fossati-Jimack
Liliane
L
Saito
Takashi
T
Walport
Mark J
MJ
Cook
H Terence
HT
D000818:Animals; D016026:Bone Marrow Transplantation; D002678:Chimera; D004198:Disease Susceptibility; D005920:Glomerular Mesangium / Q000166:cytology; D005921:Glomerulonephritis / Q000276:immunology* / Q000378:metabolism*; D007962:Leukocytes / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism*
D017452:Receptors, IgG