Therapeutic effects of prostacyclin analog on crescentic glomerulonephritis of rat.
Prostacyclin (PGI2) is known to have a relaxative action on vascular smooth muscle, an inhibitory action against platelet activation and neutrophil function. Previous studies showed the preventive effects of PGI2 on lupus nephritis and Thy-1 nephritis, although the mechanism has not been clarified. Glomerular endothelial expression of intercellular adhesion molecule-1 (ICAM-1) is up-regulated in experimental and human glomerular diseases, and is known to facilitate leukocyte infiltration into the glomeruli, which ultimately induces the various glomerular injuries. In the present study, we evaluated the therapeutic effects of PGI2 on a rat model for crescentic glomerulonephritis and investigated its putative mechanism in relation to ICAM-1-mediated leukocyte recruitment. Wistar-Kyoto (WKY) rats were injected with nephrotoxic serum and received continuous intraperitoneal infusion of PGI2. PGI2 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 along the capillary walls was not changed. Furthermore, intraglomerular expression of ICAM-1 and infiltration of macrophages were significantly suppressed by administration with PGI2. In contrast, influx of CD4 or CD8 positive cells was not altered. The present results suggest that PGI2 shows the preventive effects on experimental crescentic glomerulonephritis by inhibiting intraglomerular coagulation and ICAM-1-mediated macrophage-glomerular endothelial cell adhesive pathway.
Kushiro
M
M
Department of Medicine III, Okayama University Medical School, Japan.
Shikata
K
K
Sugimoto
H
H
Shikata
Y
Y
Miyatake
N
N
Wada
J
J
Miyasaka
M
M
Makino
H
H
D000818:Animals; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005921:Glomerulonephritis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007678:Kidney Glomerulus / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D008297:Male; D011465:Prostaglandins, Synthetic / Q000627:therapeutic use*; D011817:Rabbits; D051381:Rats; D011921:Rats, Inbred WKY
D011465:Prostaglandins, Synthetic; D018799:Intercellular Adhesion Molecule-1; C048081:beraprost; D011464:Epoprostenol