Abstract
Cellular infiltration to renal tissues is an important feature during acute puromycin aminonucleoside nephrosis (PAN) in rats. The mechanisms responsible for this infiltration are poorly understood. To elucidate the participation of adhesion molecules in PAN, nephrosis was induced in rats by intraperitoneal puromycin aminonucleoside injection. Controls represent animals injected with a 0.9% saline solution. ICAM-1 (intercellular adhesion molecule 1), CD18 (beta chain of lymphocyte-function-associated antigen), LCA (leukocyte common antigen), ED1 (monocyte/macrophage marker), and proliferating cell nuclear antigen expressions were evaluated in renal tissues 1, 2, and 7 weeks after injection. Frozen sections from PAN rat kidneys showed increased expressions of ICAM-1 and its ligand, and these findings were associated with increased levels of LCA+ and ED1+ cells in glomerulus and interstitium. The kinetics of leukocyte infiltration was similar to the kinetics of ICAM-1 expression: high values at week 2 which returned to normal values at week 7. Increased glomerular and interstitial proliferative activities (proliferating cell nulear antigen positive cells) were also found at week 2 of nephrosis. There was a correlation between ICAM-1 expression and numbers of LCA+ and ED1+ cells and between numbers of LCA+ cells and proliferating cells in glomerulus and interstitium. Correlations between glomerular and tubular ICAM-1 expression, interstitial leukocyte infiltration, and glomerular, interstitial, and tubular proliferative activities with the proteinuria were also observed during the nephrotic phase. In addition, increased lymphocyte binding to PAN renal tissues was observed, and this binding was diminished by anti-LFA-1β monoclonal antibody pretreatment of lymphocytes. A similar result was found with anti-ICAM-1 monoclonal antibody pretreatment of renal tissues. Our results suggest that increased expression of ICAM-1 and proliferative activity could be important determinants in the renal hypercellularity found in this experimental model.
Journal Section:
Original Paper
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