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 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.
Gesualdo
L
L
Institute of Nephrology, University of Bari, Italy.
Grandaliano
G
G
Ranieri
E
E
Monno
R
R
Montinaro
V
V
Manno
C
C
Schena
F P
FP
D000328:Adult; D000368:Aged; D001706:Biopsy; D015152:Blotting, Northern; D018932:Chemokine CCL2 / Q000032:analysis / Q000235:genetics* / Q000652:urine; D003449:Cryoglobulinemia / Q000276:immunology / Q000503:physiopathology*; D005260:Female; D015432:Glomerulonephritis, Membranoproliferative / Q000276:immunology / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000737:chemistry / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism
D018932:Chemokine CCL2; D012333:RNA, Messenger