International Immunology Advance Access originally published online on April 5, 2004
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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
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
receptors (FcR) in leukocytes recruitment we examined the expression of FcR in glomeruli and the effects of the administration of F(ab')2 fragment of anti-GBM antibody or FcR blocking on the initiation and progression of this model. A gradual increase of FcR 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 FcR by administering heat-aggregated IgG led to the decrease of mRNA expression for all types of FcR (types 1, 2 and 3) and a significant amelioration of glomerulonephritis manifestations. By flow cytometry and immunohistochemistry FcR2-expressing cells in glomeruli were identified as macrophages, but not CD8+ T cells. The expression of FcR1 and 3 was significantly decreased, and that of FcR2 became undetectable in CD8+ T cell-depleted rats. Thus, CD8+ T cells may stimulate FcR expression on macrophages, contributing to their glomerular accumulation and injury. These studies provide direct evidence for a crucial involvement of IgG Fc–FcR 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, FcR, macrophage
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. Smith, J. P. McDaid, G. Bhangal, R. Chawanasuntorapoj, E. S. Masuda, H. T. Cook, C. D. Pusey, and F. W.K. Tam A Spleen Tyrosine Kinase Inhibitor Reduces the Severity of Established Glomerulonephritis J. Am. Soc. Nephrol., February 1, 2010; 21(2): 231 - 236. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Bergtold, A. Gavhane, V. D'Agati, M. Madaio, and R. Clynes FcR-Bearing Myeloid Cells Are Responsible for Triggering Murine Lupus Nephritis J. Immunol., November 15, 2006; 177(10): 7287 - 7295. [Abstract] [Full Text] [PDF]
|
|