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 lupu s nephritis. The mechanism(s) underlying monocyte influx into the kidn ey 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 me sangioproliferative as well as anti-glomerular basement membrane glome rulonephritis. In the study presented here, renal MCP-1 mRNA expressio n in New Zealand Black x New Zealand White (NZB/W) F1 mice, a model of genetically determined immune complex disease that mimics systemic lu pus in humans, was investigated. Northern blot analysis revealed a sin gle 0.7 kb MCP-1 transcript of very low intensity in kidneys from 2-mo nth-old NZB/W mice that had not yet developed proteinuria nor renal da mage. 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 mi ce. By in situ hybridization, increased expression of MCP-1 mRNA was d emonstrated in glomeruli and, even more striking, in tubular epithelia l cells. Western blot analysis demonstrated increased expression of MC P-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 lo w, the influx of inflammatory cells did not appear, and glomerular and tubular structures remained well preserved. These data suggest that e levated MCP-1 might act as a signal for inflammatory cells to infiltra te the kidney in lupus nephritis.