Suppression of anti-glomerular basement membrane nephritis by administration of anti-monocyte chemoattractant protein-1 antibody in WKY rats

Abstract

Anti-glomerular basement membrane (GBM) nephritis in WKY rats is characterized by an accumulation of CD8-positive lymphocytes (CD8+lym) and monocytes/macrophages (Mo/Mφ) in the glomeruli and crescent formation. In the study presented here, the involvement of a chemokine for Mo/Mφ, monocyte chemoattractant protein-1 (MCP-1), was examined in this model. An intense induction of mRNA for MCP-1 in the glomeruli and a suppressive effect of anti-MCP-1 antibody administration on the glomerular Mo/Mφ accumulation and proteinuria were found. MCP-1 mRNA was expressed intensely in the glomeruli 4 d after the anti-GBM antibody injection. When MCP-1 was neutralized with anti-MCP-1 antibody administration, the number of Mo/Mφ infiltrating in the glomeruli decreased by 34.7% (19.6 ± 7.1 versus 30.0 ± 6.0 per glomerular cross-section, P < 0.01) and proteinuria by 66.2% (15.6 ± 9.3 versus 46.1 ± 15.1 mg/d, P < 0.01) at day 4. In contrast, the number of CD8+ lym accumulating in the glomeruli was not affected significantly (6.6 ± 2.7 versus 6.0 ± 3.0 per glomerular cross-section, P > 0.05). However, the treatment with the anti-MCP-1 antibody did not reduce Mo/Mφ infiltration, urinary protein excretion, and crescent formation at day 8. These data suggest that MCP-1 plays a role in the glomerular accumulation of Mo/Mφ, and that the infiltrating Mo/Mφ cause glomerular injury and increased excretion of protein in the urine.