title: Fc receptor-mediated accumulation of macrophages in crescentic glomerulonephritis induced by anti-glomerular basement membrane antibody administration in WKY rats.
abstract: Anti-glomerular basement membrane (GBM) glomerulonephritis induced in WKY rats is characterized by glomerular accumulation of CD8(+) T cells and monocytes/macrophages, followed by crescent formation. The mechanism of leukocyte accumulation after antibody binding to GBM is still unclear. To unveil an involvement of Fcgamma receptors (FcgammaR) in leukocytes recruitment we examined the expression of FcgammaR in glomeruli and the effects of the administration of F(ab')(2) fragment of anti-GBM antibody or FcgammaR blocking on the initiation and progression of this model. A gradual increase of FcgammaR mRNA expression in glomeruli during the time course of disease suggested their significance in the development of glomerulonephritis. Glomerular lesions and proteinuria were induced only in rats injected with intact IgG of anti-GBM antibody, but not with the F(ab')(2) fragment. In vivo blocking of FcgammaR by administering heat-aggregated IgG led to the decrease of mRNA expression for all types of FcgammaR (types 1, 2 and 3) and a significant amelioration of glomerulonephritis manifestations. By flow cytometry and immunohistochemistry FcgammaR2-expressing cells in glomeruli were identified as macrophages, but not CD8(+) T cells. The expression of FcgammaR1 and 3 was significantly decreased, and that of FcgammaR2 became undetectable in CD8(+) T cell-depleted rats. Thus, CD8(+) T cells may stimulate FcgammaR expression on macrophages, contributing to their glomerular accumulation and injury. These studies provide direct evidence for a crucial involvement of IgG Fc-FcgammaR interaction in glomerular recruitment of macrophages and following induction of anti-GBM glomerulonephritis in WKY rats.
authors.affiliation: Department of Structural Pathology, Institute of Nephrology, Japan.
authors.forename: Pavel
authors.initials: P
authors.lastname: Kovalenko
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Fujinaka
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kawamura
authors.forename: Zhenyun
authors.initials: Z
authors.lastname: Qu
authors.forename: Adel Galal Ahmed
authors.initials: AG
authors.lastname: El-Shemi
authors.forename: Huiping
authors.initials: H
authors.lastname: Li
authors.forename: Asako
authors.initials: A
authors.lastname: Matsuki
authors.forename: Vladimir
authors.initials: V
authors.lastname: Bilim
authors.forename: Eishin
authors.initials: E
authors.lastname: Yaoita
authors.forename: Toru
authors.initials: T
authors.lastname: Abo
authors.forename: Makoto
authors.initials: M
authors.lastname: Uchiyama
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D001485:Basement Membrane / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000648:ultrastructure; D004195:Disease Models, Animal; D005434:Flow Cytometry; D015870:Gene Expression; D015433:Glomerulonephritis, Membranous / Q000209:etiology / Q000276:immunology*; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007678:Kidney Glomerulus / Q000648:ultrastructure; D008212:Lymphocyte Depletion; D008264:Macrophages / Q000276:immunology* / Q000648:ultrastructure; D008856:Microscopy, Fluorescence; D011507:Proteinuria / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011921:Rats, Inbred WKY; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D012333:RNA, Messenger; D017452:Receptors, IgG