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- Title
Nephrotoxic nephritis is mediated by Fcγ receptors on circulating leukocytes and not intrinsic renal cells.
- Authors
Tarzi, Ruth M.; Davies, Kevin A.; Robson, Michael G.; Fossati-Jimack, Liliane; Saito, Takashi; Walport, Mark J.; Cook, H. Terence
- Abstract
Nephrotoxic nephritis is mediated by Fcγ receptors on circulating leukocytes and not intrinsic renal cells. Background. There is evidence that mesangial cells express Fcγ receptors in vitro, but the in vivo relevance of this is not known. FcRγ-/- mice lack the gamma chain signaling subunit and therefore do not express the activator Fcγ receptors (FcγRI and FcγRIII) or the high affinity IgE receptor, FcεRI. FcRγ-/- 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 Fcγ 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 FcRγ. Donor marrow reconstitution was confirmed by flow cytometric analysis of peripheral blood for FcγRIII, and the susceptibility of the transplanted mice to accelerated nephrotoxic nephritis was tested. Results. Following the induction of nephrotoxic nephritis, FcRγ-/- 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 FcRγ-/- marrow were completely protected from glomerular crescents, thrombosis, albuminuria and renal impairment, as were FcRγ-/- mice transplanted with FcRγ-/- marrow. Mice with FcRγ-/- marrow had prolonged survival, but by day 28 after nephrotoxic serum injection they had developed mesangial hypercellularity and a macrophage influx caused by non-FcRγ dependent mechanisms. Conclusion. Despite previous evidence that mesangial cells express Fcγ receptors in vitro, they have no role in an FcRγ-dependent model of glomerulonephritis in vivo.
- Subjects
KIDNEY diseases; NEPHROTOXICOLOGY; LEUCOCYTES
- Publication
Kidney International, 2002, Vol 62, Issue 6, p2087
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1046/j.1523-1755.2002.00687.x