INTERVENTION OF CRESCENTIC GLOMERULONEPHRITIS BY ANTIBODIES TO MONOCYTE CHEMOTACTIC AND ACTIVATING FACTOR (MCAF MCP-1)/

We investigated the pathophysiological cole of a potent macrophage (M phi) chemotactic cytokine (chemokine), monocyte chemotactic and activa ting factor/monocyte chemoattractant protein-1 (MCAF/MCP-1), in an ani mal model of crescentic glomerulonephritis. Administration of a small dose of nephrotoxic sera induced severe proliferative and necrotizing glomerulonephritis, with crescentic formation in the early phase and g lomerulosclerosis in the later phase, in Wistar-Kyoto rats. MCAF/MCP-1 protein was detected immunohistochemic ally in glomeruli, vascular en dothelial cells, and tubular epithelial cells in the early phase of in jured kidney tissues but not in normal ones. Anti-MCAF/MCP-1 antibodie s decreased the number of M phi in glomeruli, and prevented crescentic formation and the fusion of epithelial cell foot process in nephritic rats, thereby decreasing the excreted amounts of protein to normal le vels on days 3 and 6. Furthermore, anti-MCAF/MCP-1 antibodies remarkab ly reduced glomerulosclerosis and improved renal dysfunction as well a s proteinuria in the later phase (56 days). These results indicate tha t MCAF/MCP-1 essentially participates in the impairment of renal funct ions associated with crescentic glomerulonephritis by recruiting and a ctivating M phi.