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PMID: 9546786 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

Nature medicine ·Vol. 4 ·No. 4 ·1998-04-00 ·Pages 415-20

Sata M, Walsh K

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.

MeSH Terms
Aorta Apoptosis Cell Adhesion/drug effects,physiology Cell Survival/drug effects,physiology Cells, Cultured Chromatin/ultrastructure Coculture Techniques DNA Fragmentation Endothelium, Vascular/cytology,drug effects,physiology Fas Ligand Protein Gene Expression Regulation/drug effects Humans Leukocytes/physiology Leukocytes, Mononuclear/physiology Membrane Glycoproteins/biosynthesis Microcirculation Tumor Necrosis Factor-alpha/pharmacology Umbilical Veins fas Receptor/physiology
Chemicals
Chromatin FASLG protein, human Fas Ligand Protein Membrane Glycoproteins Tumor Necrosis Factor-alpha fas Receptor
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Sata M
Division of Cardiovascular Research, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Massachusetts 02135, USA.
Walsh K
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Article Info
Journal
Nature medicine
Abbr.
Nat Med
ISSN
1078-8956
DOI
10.1038/nm0498-415
Published
1998-04-00
Pages
415-20
Language
English
Region
United States
NLM ID
9502015
PMCID
PMC2828686
Subset
IM
Grants
NIA NIH HHS · R01 AG015052-02 · United States
NHLBI NIH HHS · HL50692 · United States
NIAMS NIH HHS · AR40197 · United States
NHLBI NIH HHS · R01 HL050692-10 · United States
NIA NIH HHS · R01 AG015052 · United States
NIA NIH HHS · AG15052 · United States
NIA NIH HHS · R37 AG015052 · United States
NIAMS NIH HHS · R01 AR040197 · United States
NIAMS NIH HHS · R01 AR040197-11 · United States
External Links
PubMed source DOI: 10.1038/nm0498-415 PMC Full Text View journal details
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