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International Immunology Advance Access originally published online on April 5, 2004
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International Immunology, Vol. 16, No. 5, pp. 625-634, May 2004
© 2004 Japanese Society for Immunology

Fc receptor-mediated accumulation of macrophages in crescentic glomerulonephritis induced by anti-glomerular basement membrane antibody administration in WKY rats

Pavel Kovalenko1, Hidehiko Fujinaka1, Yutaka Yoshida1, Hiroki Kawamura2, Zhenyun Qu1, Adel Galal Ahmed El-Shemi1, Huiping Li1, Asako Matsuki1, Vladimir Bilim1, Eishin Yaoita1, Toru Abo2, Makoto Uchiyama3 and Tadashi Yamamoto1

1 Department of Structural Pathology, Institute of Nephrology, 2 Division of Immunology and Zoology, Department of Infectious Disease Control, Course for Community Disease Control and 3 Division of Pediatrics, Department of Homeostatic Regulation and Development, Course for Biological Functions and Medical Control, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan

Correspondence to: T. Yamamoto; E-mail: tdsymmt{at}med.niigata-u.ac.jp
Transmitting editor: K. Okumura

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 Fc{gamma} receptors (Fc{gamma}R) in leukocytes recruitment we examined the expression of Fc{gamma}R in glomeruli and the effects of the administration of F(ab')2 fragment of anti-GBM antibody or Fc{gamma}R blocking on the initiation and progression of this model. A gradual increase of Fc{gamma}R 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 Fc{gamma}R by administering heat-aggregated IgG led to the decrease of mRNA expression for all types of Fc{gamma}R (types 1, 2 and 3) and a significant amelioration of glomerulonephritis manifestations. By flow cytometry and immunohistochemistry Fc{gamma}R2-expressing cells in glomeruli were identified as macrophages, but not CD8+ T cells. The expression of Fc{gamma}R1 and 3 was significantly decreased, and that of Fc{gamma}R2 became undetectable in CD8+ T cell-depleted rats. Thus, CD8+ T cells may stimulate Fc{gamma}R expression on macrophages, contributing to their glomerular accumulation and injury. These studies provide direct evidence for a crucial involvement of IgG Fc–Fc{gamma}R interaction in glomerular recruitment of macrophages and following induction of anti-GBM glomerulonephritis in WKY rats.

Keywords: anti-glomerular basement membrane antibody, CD8+ T cell, crescentic glomerulonephritis, Fc{gamma}R, macrophage


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