Abstract
Herein we show that exposure of human umbilical vein endothelial cells to tumor necrosis factor alpha (TNFalpha) led to platelet endothelial cell adhesion molecule-1 (PECAM1) surface redistribution, disruption of cytoskeleton connections, and increased PECAM1 phosphorylation, accompanied by increased permeability to macromolecules. The in vitro use of inhibitors of tyrosine or serine-threonine kinases could prevent both PECAM1 surface redistribution and the increase in permeability induced by the cytokine. In vivo administration of lavendustin A, a natural tyrosine kinase inhibitor, protected endothelial cells from TNFalpha-dependent vascular leakage in mouse liver. We propose that the involvement of PECAM1 in TNFalpha-mediated effects on vascular permeability may depend on a dynamically regulated cytoskeletal association, related to the degree of PECAM1 phosphorylation.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Alkaloids / pharmacology
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Antigens, Differentiation, Myelomonocytic / metabolism*
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Benzoquinones
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Capillary Permeability / drug effects*
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Cell Adhesion Molecules / metabolism*
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Cell Compartmentation
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Cells, Cultured
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Endothelium, Vascular / metabolism*
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Enzyme Inhibitors / pharmacology
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Fluorescent Antibody Technique, Indirect
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Gene Expression
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Humans
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Lactams, Macrocyclic
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Phosphorylation
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Platelet Endothelial Cell Adhesion Molecule-1
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Protein Kinase Inhibitors
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Quinones / pharmacology
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RNA, Messenger / genetics
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Rifabutin / analogs & derivatives
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Staurosporine
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Tumor Necrosis Factor-alpha / pharmacology*
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Umbilical Veins
Substances
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Alkaloids
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Antigens, Differentiation, Myelomonocytic
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Benzoquinones
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Cell Adhesion Molecules
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Enzyme Inhibitors
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Lactams, Macrocyclic
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Platelet Endothelial Cell Adhesion Molecule-1
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Protein Kinase Inhibitors
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Quinones
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RNA, Messenger
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Tumor Necrosis Factor-alpha
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Rifabutin
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herbimycin
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Staurosporine