INTERCELLULAR-ADHESION MOLECULE-1 MEDIATES MONONUCLEAR CELL INFILTRATION INTO RAT GLOMERULI AFTER RENAL ABLATION

Mononuclear cells, primarily macrophages and lymphocytes, infiltrate t he renal glomeruli and are involved in the progression of various glom erular diseases. Intercellular adhesion molecule 1 (ICAM-1) is express ed on the vascular endothelium and mediates the infiltration of leukoc ytes into the site of inflammation. Although the expression of ICAM-1 can be induced by the stimulation of inflammatory cytokine, ICAM-1 exp ression can also be induced by such nonimmune mechanisms as shear stre ss. Glomerular hyperfiltration is a major mechanism that contributes t o the progression of the glomerular sclerosis that results from the lo ss of functioning nephrons. In the present study, we examined the role of ICAM-1 for mononuclear cell infiltration in the glomeruli of the f ive-sixth nephrectomized rat as a model of glomerular hyperfiltration. The fluorescence intensity score of the staining for ICAM-1 in the gl omeruli of the five-sixth nephrectomized rats was significantly increa sed as compared with that in the control (sham-operated) rats at 1 wee k (1.51 +/- 0.15 vs. 0.61 +/- 0.13; p < 0.01) and 2 weeks (1.31 +/- 0. 17 vs. 0.51 +/- 0.09; p < 0.01). The number of leukocytes present in t he glomeruli was significantly increased in the five-sixth nephrectomi zed rats compared with control (sham-operated) rats at 1 week (3.44 +/ - 0.16 vs. 0.99 +/- 0.08; p < 0.01) and 2 weeks (3.14 +/- 0.14 vs. 0.8 9 +/- 0.07; p < 0.01). Leukocytes mainly consisted of macrophages in t he five-sixth nephrectomized rats at 1 week (2.39 +/- 0.19) and 2 week s (1.46 +/- 0.11). Anti-ICAM-1 monoclonal antibody effectively prevent ed the infiltration of macrophages into the glomeruli following nephre ctomy. These results indicate that glomerular hyperfiltration may be i nvolved in the induction of the expression of ICAM-1 and the infiltrat ion of macrophages into the renal glomeruli following glomerular injur y.