Renal expression of monocyte chemoattractant protein-1 in lupus autoimmune mice.
Mononuclear cell infiltration in glomeruli and renal interstitium is a prominent feature of some types of glomerulonephritis, including lupus nephritis. The mechanism(s) underlying monocyte influx into the kidney is not fully understood. Recently, monocyte chemoattractant protein-1 (MCP-1) has been identified as a chemotactic factor involved in the recruitment of monocytes/macrophages in the glomeruli of rats with mesangioproliferative as well as anti-glomerular basement membrane glomerulonephritis. In the study presented here, renal MCP-1 mRNA expression in New Zealand Black x New Zealand White (NZB/W) F1 mice, a model of genetically determined immune complex disease that mimics systemic lupus in humans, was investigated. Northern blot analysis revealed a single 0.7 kb MCP-1 transcript of very low intensity in kidneys from 2-month-old NZB/W mice that had not yet developed proteinuria nor renal damage. Message levels, which increased markedly with the progression of nephritis and in association with mononuclear cell infiltration, were 10- and 15- fold higher in 8-10-month-old mice than in 2-month-old mice. By in situ hybridization, increased expression of MCP-1 mRNA was demonstrated in glomeruli and, even more striking, in tubular epithelial cells. Western blot analysis demonstrated increased expression of MCP-1 protein in kidneys of 10-month-old NZB/W mice, consistent with MCP-1 mRNA data. When NZB/W mice were treated with cyclophosphamide up to 12 months of age, expression of MCP-1 in the renal tissue remained low, the influx of inflammatory cells did not appear, and glomerular and tubular structures remained well preserved. These data suggest that elevated MCP-1 might act as a signal for inflammatory cells to infiltrate the kidney in lupus nephritis.
Zoja
C
C
Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
Liu
X H
XH
Donadelli
R
R
Abbate
M
M
Testa
D
D
Corna
D
D
Taraboletti
G
G
Vecchi
A
A
Dong
Q G
QG
Rollins
B J
BJ
Bertani
T
T
Remuzzi
G
G
D000818:Animals; D001327:Autoimmune Diseases / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D003520:Cyclophosphamide / Q000494:pharmacology; D005260:Female; D015870:Gene Expression; D007166:Immunosuppressive Agents / Q000494:pharmacology; D017403:In Situ Hybridization; D007668:Kidney / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008177:Lupus Vulgaris / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008814:Mice, Inbred NZB; D011507:Proteinuria / Q000652:urine; D013997:Time Factors
D018932:Chemokine CCL2; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide