MONOCYTE RECRUITMENT IN CRYOGLOBULINEMIC MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS - A PATHOGENETIC ROLE FOR MONOCYTE CHEMOTACTIC PEPTIDE-1

Monocyte chemotactic peptide-1 (MCP-1) belongs to a large family of cy tokines known as chemokines. It is a potent mediator of inflammatory r esponse and is thought to play a major role in recruiting monocytes in to the site of inflammation. Mixed cryoglobulinemia is a systemic vasc ulitis characterized in 20 to 30% of the cases by renal involvement. M onocyte infiltration into the glomerulus, and in the periglomerular an d perivascular areas is a common histopathological feature of this for m of glomerulonephritis. We sought to determine, by in situ hybridizat ion and immunohistochemistry, the renal gene and protein expression of MCP-1 in cryoglobulinemic glomerulonephritis compared to normal kidne y, and to correlate it with macrophage infiltration. Kidney biopsy spe cimens were obtained from 9 patients with cryoglobulinemic glomerulone phritis and 9 control kidneys. The distribution and intensity of MCP-1 gene and protein expression, and the macrophage infiltration (CD68 po sitive cells) were evaluated and quantitated by a computerized image a nalysis system. In normal kidneys, MCP-1 was weakly expressed, both at the gene as well as at the protein level. In diseased kidneys, a stat istically significant (P < 0.001) up-regulation of MCP-I gene and prot ein expression was found, particularly within the areas of tubulointer stitial damage and the glomeruli. By means of CD68 positive cells, a s ignificant correlation (P < 0.001) was found between glomerular, tubul ointerstitial macrophage infiltration and MCP-I expression. Moreover, by combining immunohistochemistry and in situ hybridization, we observ ed the presence of CD68 positive cells mainly, if not exclusively, aro und the cells expressing MCP-1 mRNA Interestingly, a striking increase in MCP-1 urinary concentration was found in cryoglobulinemic patients . In conclusion, our data suggest that MCP-1 may play a major role in modulating the inflammatory process observed in cryoglobulinemic glome rulonephritis.