[Antinephritis effect of anti-ICAM-1 monoclonal antibody and anti-LFA-1 monoclonal antibody on accelerated-type anti-GBM nephritis in rats].
The involvement of adhesion molecules in the accumulation of inflammatory cells in the glomeruli and subsequent glomerular injury was examined in accelerated-type anti-GBM nephritis in rats. This animal model is known to be manifested by progressive and irreversible glomerular damage with rapid influx of monocytes/macrophages into the glomeruli. Up-regulated expression of intercellular adhesion molecule-1 (ICAM-1) was observed exclusively in the glomerular endothelial cells in this model. Therefore we examined the effect of ICAM-1 and lymphocyte function-associated antigen-1 (LFA-1) in the pathogenesis of this nephritis. Four groups of rats with accelerated-type anti-GBM nephritis were investigated. The first group was the control group injected with normal mouse IgG 2mg/Kg. The second group was administered mouse anti-rat ICAM-1 monoclonal antibody (1A-29) 2 mg/Kg. The third group was administered mouse anti-rat LFA-1 beta monoclonal antibody (WT-3) 2mg/Kg. The fourth group received both 1A-29 1mg and WT-3 1mg/Kg. Proteinuria and the influx of monocytes/macrophage in this model were decreased after the administration of 1A-29 or WT-3. Simultaneous administration of both antibodies showed intense suppression of the proteinuria and marked reduction of the infiltrating cells. These results suggested that the ICAM-1/LFA-1 pathway is critically involved in the pathogenesis of accelerated-type anti-GBM nephritis in rats.
Kawamura
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Department of Immunology, Juntendo University, School of Medicine, Tokyo, Japan.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001485:Basement Membrane / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology*; D005921:Glomerulonephritis / Q000276:immunology / Q000628:therapy*; D018799:Intercellular Adhesion Molecule-1; D007678:Kidney Glomerulus / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1