Expression of Fas and Fas ligand on mouse renal tubular epithelial cells in the generalized Shwartzman reaction and its relationship to apoptosis

Previously we reported that the consecutive injection of lipopolysaccharide (LPS) into LPS-sensitized mice for the generalized Shwartzman reaction (GS R) appeared to induce the injury of renal tubular epithelial cells via apop tosis. The aim of this study was to characterize the mechanism of renal tub ular epithelial cell injury in GSR. The expression of Fas and Fas ligand wa s immunohistochemically detected on renal tubular epithelial cells from GSR -induced mice, although neither Fas nor Fas ligand was found in cells from untreated control mice or in cells from mice receiving a single injection o f LPS. GSR-induced renal tubular epithelial cell injury was produced in nei ther Fas-negative MRL-lpr/lpr mice nor Pas ligand-negative MRL-gld/gld mice . The administration of anti-gamma interferon antibody together with a prep arative injection of LPS prevented the expression of Fas and Fas ligand and the apoptosis of renal tubular epithelial cells. A provocative injection o f tumor necrosis factor alpha into LPS-sensitized mice augmented Fas and Fa s ligand expression and the apoptosis of renal tubular epithelial cells. Th e administration of tumor necrosis factor alpha to interleukin-12-sensitize d mice resulted in Fas and Fas ligand expression and the apoptosis. Sensiti zation with interleukin-12 together with anti-gamma interferon antibody did not cause the apoptosis of renal tubular epithelial cells. It was suggeste d that the Fas/Fas ligand system probably plays a critical role in the deve lopment of renal tubular epithelial cell injury through apoptotic cell deat h.