Glomerular expression of monocyte chemoattractant protein-1 in experimental and human glomerulonephritis.

BACKGROUND

Glomerular monocytes are found in a variety of renal diseases and appear to be important in the pathogenesis of glomerular injury. The mediators responsible for recruiting monocytes to the glomerulus are not well characterized. We have recently established that cultured human mesangial cells produce the specific monocyte chemoattractant, monocyte chemoattractant protein-1 (MCP-1) in response to inflammatory 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 regarding the expression of MCP-1 during renal disease. The present study was undertaken to investigate the in vivo expression of MCP-1 during experimental and human GN.

EXPERIMENTAL DESIGN

A rodent model of anti-glomerular basement membrane GN was used to investigate glomerular MCP-1 mRNA regulation and protein expression. The presence of MCP-1 in human renal tissue was studied by immunostaining kidney biopsy material from patients with a variety of glomerulopathies.

RESULTS

MCP-1 mRNA was transiently upregulated during the early stages of experimental GN. Message levels increased in association with the monocyte influx and correlated with expression of immunoreactive MCP-1 in the nephritic glomeruli. Glomerular MCP-1 was also found in human inflammatory glomerulopathies, but not in glomerular diseases lacking a prominent monocyte infiltrate.

CONCLUSIONS

These data support a role for MCP-1 in the pathogenesis of glomerular inflammation.