Expression of monocyte chemoattractant protein-1 in experimental crescentic glomerulonephritis in rats.

Crescentic glomerulonephritis (CGN) is a rapidly progressive glomerular disease that is usually associated with a poor prognosis. Monocytes/macrophages are frequently observed in glomeruli in cases of CGN, and they are considered to play a crucial role in the pathogenesis of this disease. In this study we analyzed the glomerular expression of monocyte chemoattractant protein-1 (MCP-1), a potent chemoattractant for monocytes, in an experimental model of CGN. A model of the disease was induced in the WKY strain of rats by intravenous injection of antiserum raised against glomerular basement membranes. Accumulation of monocytes/macrophages in glomeruli was observed 4 hours after the injection of antiserum. Northern blot analysis showed that the expression of mRNA for MCP-1 was enhanced within 4 hours, peaked on day 3--when it was 60 times that in the control--and then declined. Immunostaining with MCP-1-specific antibody revealed the expression of MCP-1 protein in the diseased glomeruli but not in control glomeruli. Quantitative analysis of glomerular MCP-1 protein by enzyme-linked immunosorbent assay revealed a level 46 times that in the control in reflecting the increase in mRNA for MCP-1. These results indicate that glomeruli of rats with CGN produce MCP-1, which may play an important role in the pathogenesis of glomerular inflammation and crescent formation in CGN.