THERAPEUTIC EFFECTS OF PROSTACYCLIN ANALOG ON CRESCENTIC GLOMERULONEPHRITIS OF RAT

Prostacyclin (PGI(2)) is known to have a relaxative action on vascular smooth muscle, an inhibitory action against platelet activation and n eutrophil function. Previous studies showed the preventive effects of PGI(2) on lupus nephritis and Thy-1 nephritis, although the mechanism has not been clarified. Glomerular endothelial expression of intercell ular adhesion molecule-1 (ICAM-1) is up-regulated in experimental and human glomerular diseases, and is known to facilitate leukocyte infilt ration into the glomeruli, which ultimately induces the various glomer ular injuries. In the present study, we evaluated the therapeutic effe cts of PGI(2) tin a rat model for crescentic glomerulonephritis and in vestigated its putative mechanism in relation to ICAM-1-mediated leuko cyte recruitment. Wistar-Kyoto (WKY) rats were injected with nephrotox ic serum and received continuous intraperitoneal infusion of PGI(2). P GI(2) dramatically decreased proteinuria (123.0 +/- 18.8 vs. 31.6 +/- 4.5), crescent formation and deposition of fibrinogen in the glomeruli , while the deposition of rabbit IgG, rat IgG and rat C3 alone the cap illary walls was not changed. Furthermore, intraglomerular expression of ICAM-1 and infiltration of macrophages were significantly suppresse d by administration with PGI(2). In contrast, influx of CD4 or CD8 pos itive cells was not altered. The present results suggest that PGI(2) s hows the preventive effects on experimental crescentic glomerulonephri tis by inhibiting intraglomerular coagulation and ICAM-1-mediated macr ophage-glomerular endothelial cell adhesive pathway.