EXPRESSION AND LOCALIZATION OF CYCLOOXYGENASE ISOFORMS AND CYTOSOLIC PHOSPHOLIPASE-A2 IN ANTI-THY-1 GLOMERULONEPHRITIS

Glomerular expression of the major rate-limiting enzymes for prostanoi d synthesis, cyclooxygenase isoforms (COX-1 and COX-2) and cytosolic p hospholipase A2 (cPLA2), was investigated in anti-Thy-1 nephritis in r ats. Ribonuclease protection assay demonstrated minimal COX-1 mRNA exp ression in glomeruli of control rat kidneys and a gradual increase of expression from day 1 to day 10 after administration of monoclonal ant i-rat Thy-1 antibody. On the other hand, COX-2 mRNA expression, also m inimal in the normal glomeruli, was enhanced in a biphasic pattern wit h two peaks at 1 h and day 10. Expression of cPLA2 mRNA, which was und etectable in normal glomeruli, was induced on day 1 and increased grad ually in a pattern similar to that of COX-1 mRNA expression. Immunoflu orescence microscopy, using antibodies against COX isoforms, showed th at both COX-1 and COX-2 were negligible or faintly detectable in the g lomeruli of control rat kidneys. In contrast, the immunofluorescence f or COX-1 was intensified on days 4 and 10 along the glomerular capilla ry walls probably in glomerular epithelial and/or endothelial cells, w hereas COX-2 staining was exclusively enhanced in the glomerular epith elial cells at 1 h and day 10 during the course of anti-Thy-1 nephriti s. These findings indicate that prostanoids generated through inductio n of COX-1, COX-2, and cPLA2 are implicated in the mediation of the me sangial cell injury model. In particular, the upregulation of COX-2 ex pression in glomerular epithelial cells in the selective mesangial cel l injury model suggests an intercellular interaction between mesangial cells and glomerular epithelial cells.