title: Tumor necrosis factor alpha-induced vascular leakage involves PECAM1 phosphorylation.
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.
authors.affiliation: Laboratory of Tumor Immunology, Scientific Institute San Raffaele, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Ferrero
authors.forename: A
authors.initials: A
authors.lastname: Villa
authors.forename: M E
authors.initials: ME
authors.lastname: Ferrero
authors.forename: E
authors.initials: E
authors.lastname: Toninelli
authors.forename: J R
authors.initials: JR
authors.lastname: Bender
authors.forename: R
authors.initials: R
authors.lastname: Pardi
authors.forename: M R
authors.initials: MR
authors.lastname: Zocchi
mesh_terms: D000470:Alkaloids / Q000494:pharmacology; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism*; D016227:Benzoquinones; D002199:Capillary Permeability / Q000187:drug effects*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002451:Cell Compartmentation; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019084:Fluorescent Antibody Technique, Indirect; D015870:Gene Expression; D006801:Humans; D047029:Lactams, Macrocyclic; D010766:Phosphorylation; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D047428:Protein Kinase Inhibitors; D011809:Quinones / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D017828:Rifabutin / Q000031:analogs & derivatives; D019311:Staurosporine; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014471:Umbilical Veins
chemical_list: D000470:Alkaloids; D015214:Antigens, Differentiation, Myelomonocytic; D016227:Benzoquinones; D015815:Cell Adhesion Molecules; D004791:Enzyme Inhibitors; D047029:Lactams, Macrocyclic; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D047428:Protein Kinase Inhibitors; D011809:Quinones; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D017828:Rifabutin; C020754:herbimycin; D019311:Staurosporine