TNFα regulation of Fas ligand expression on the vascular endothelium modulates leukocyte extravasation

It is generally believed that the vascular endothelium serves as an inflammatory barrier by providing a nonadherent surface to leukocytes. Here, we report that Fas ligand (FasL) is expressed on vascular endothelial cells (ECs) and that it may function to actively inhibit leukocyte extravasation. TNF alpha downregulates FasL expression with an accompanying decrease in EC cytotoxicity toward co-cultured Fas-bearing cells. Local administration of TNF alpha to arteries down regulates endothelial Fast expression and induces mononuclear cell infiltration. Constitutive Fast expression markedly attenuates TNF alpha-induced cell infiltration and adherent mononuclear cells undergo apoptosis under these conditions. These findings suggest that endothelial Fast expression can negatively regulate leukocyte extravasation.