Monocyte recruitment in cryoglobulinemic membranoproliferative glomerulonephritis: a pathogenetic role for monocyte chemotactic peptide-1

Kidney Int. 1997 Jan;51(1):155-63. doi: 10.1038/ki.1997.19.


Monocyte chemotactic peptide-1 (MCP-1) belongs to a large family of cytokines known as chemokines. It is a potent mediator of inflammatory response and is thought to play a major role in recruiting monocytes into the site of inflammation. Mixed cryoglobulinemia is a systemic vasculitis characterized in 10 to 30% of the cases by renal involvement. Monocyte infiltration into the glomerulus, and in the periglomerular and perivascular areas is a common histopathological feature of this form of glomerulonephritis. We sought to determine, by in situ hybridization and immunohistochemistry, the renal gene and protein expression of MCP-1 in cryoglobulinemic glomerulonephritis compared to normal kidney, and to correlate it with macrophage infiltration. Kidney biopsy specimens were obtained from 9 patients with cryoglobulinemic glomerulonephritis and 9 control kidneys. The distribution and intensity of MCP-1 gene and protein expression, and the macrophage infiltration (CD68 positive cells) were evaluated and quantitated by a computerized image analysis system. In normal kidneys, MCP-1 was weakly expressed, both at the gene as well as at the protein level. In diseased kidneys, a statistically significant (P < 0.001) up-regulation of MCP-1 gene and protein expression was found, particularly within the areas of tubulointerstitial damage and the glomeruli. By means of CD68 positive cells, a significant correlation (P < 0.001) was found between glomerular, tubulointerstitial macrophage infiltration and MCP-1 expression. Moreover, by combining immunohistochemistry and in situ hybridization, we observed the presence of CD68 positive cells mainly, if not exclusively, around 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 glomerulonephritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biopsy
  • Blotting, Northern
  • Chemokine CCL2 / analysis
  • Chemokine CCL2 / genetics*
  • Chemokine CCL2 / urine
  • Cryoglobulinemia / immunology
  • Cryoglobulinemia / physiopathology*
  • Female
  • Glomerulonephritis, Membranoproliferative / immunology
  • Glomerulonephritis, Membranoproliferative / pathology*
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Male
  • Middle Aged
  • Monocytes / chemistry
  • Monocytes / immunology*
  • RNA, Messenger / metabolism


  • Chemokine CCL2
  • RNA, Messenger