title: TNFalpha regulation of Fas ligand expression on the vascular endothelium modulates leukocyte extravasation.
abstract: 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. TNFalpha downregulates FasL expression with an accompanying decrease in EC cytotoxicity toward co-cultured Fas-bearing cells. Local administration of TNFalpha to arteries downregulates endothelial FasL expression and induces mononuclear cell infiltration. Constitutive FasL expression markedly attenuates TNFalpha-induced cell infiltration and adherent mononuclear cells undergo apoptosis under these conditions. These findings suggest that endothelial FasL expression can negatively regulate leukocyte extravasation.
authors.affiliation: Division of Cardiovascular Research, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Massachusetts 02135, USA.
authors.forename: M
authors.initials: M
authors.lastname: Sata
authors.forename: K
authors.initials: K
authors.lastname: Walsh
mesh_terms: D001011:Aorta; D017209:Apoptosis; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002843:Chromatin / Q000648:ultrastructure; D018920:Coculture Techniques; D053938:DNA Fragmentation; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D053222:Fas Ligand Protein; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007962:Leukocytes / Q000502:physiology*; D007963:Leukocytes, Mononuclear / Q000502:physiology; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D008833:Microcirculation; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014471:Umbilical Veins; D019014:fas Receptor / Q000502:physiology*
chemical_list: D002843:Chromatin; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor