GLOMERULAR EXPRESSION OF MONOCYTE CHEMOATTRACTANT PROTEIN-1 IN EXPERIMENTAL AND HUMAN GLOMERULONEPHRITIS

BACKGROUND: Glomerular monocytes are found in a variety of renal disea ses and appear to be important in the pathogenesis of glomerular injur y, The mediators responsible for recruiting monocytes to the glomerulu s are not well characterized, We have recently established that cultur ed human mesangial cells produce the specific monocyte chemoattractant , monocyte chemoattractant protein-1 (MCP-1) in response to inflammato ry cytokines commonly found in glomeruli during glomerulonephritis (GN ). This suggested that MCP-1 may be involved in recruiting leukocytes to the glomerulus. To date however, there is little information regard ing the expression of MCP-1 during renal disease. The present study wa s undertaken to investigate the in vivo expression of MCP-1 during exp erimental and human GN. EXPERIMENTAL DESIGN: A rodent model of anti-gl omerular basement membrane GN was used to investigate glomerular MGP-1 mRNA regulation and protein expression. The presence of MCP-1 in huma n renal tissue was studied by immunostaining kidney biopsy material fr om patients with a variety of glomerulopathies. RESULTS: MCP-1 mRNA wa s transiently upregulated during the early stages of experimental GN. Message levels increased in association with the monocyte influx and c orrelated with expression of immunoreactive MCP-1 in the nephritic glo meruli. Glomerular MCP-1 was also found in human inflammatory glomerul opathies, but not in glomerular diseases lacking a prominent monocyte infiltrate. CONCLUSIONS: These data support a role for MCP-1 in the pa thogenesis of glomerular inflammation.