title: Tumor necrosis factor alters cytoskeletal organization and barrier function of endothelial cells.
abstract: Treatment of human umbilical cord vein endothelial cells with tumor necrosis factor results in marked changes in cell shape and cytoskeletal organization. After 4 h of treatment, these cells loose reciprocal contacts with the formation of intercellular gaps. This retraction reaches a maximum after 6 h when most stress fibers staining for F-actin disappear and vinculin becomes diffused in the cytoplasm. Such changes spontaneously reverse after 24 h in the presence of tumor necrosis factor or after 2 h of incubation in fresh medium. After treatment with tumor necrosis factor, endothelial monolayers become permeable to albumin because of gaps that form between cells. Normal human serum, plasma alpha 1-proteinase inhibitor and an anti-inflammatory peptide that decrease synthesis of platelet-activating factor inhibit the changes induced by tumor necrosis factor. Furthermore, receptor antagonists of platelet-activating factor have the same effect. These findings suggest that platelet-activating factor is a secondary mediator responsible for the changes in cell shape and cytoskeletal organization, and for the leakiness of endothelial monolayers.
authors.affiliation: Dipartimento di Biochimica e Biofisica, 1 Facoltà di Medicina, Università di Napoli, Italia.
authors.forename: G
authors.initials: G
authors.lastname: Camussi
authors.forename: E
authors.initials: E
authors.lastname: Turello
authors.forename: F
authors.initials: F
authors.lastname: Bussolino
authors.forename: C
authors.initials: C
authors.lastname: Baglioni
mesh_terms: D000595:Amino Acid Sequence; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides; D002463:Cell Membrane Permeability; D003598:Cytoskeletal Proteins / Q000276:immunology; D004730:Endothelium, Vascular / Q000166:cytology* / Q000276:immunology; D005455:Fluorescent Antibody Technique; D006801:Humans; D007301:Insect Hormones / Q000494:pharmacology; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D023181:Antimicrobial Cationic Peptides; D003598:Cytoskeletal Proteins; D007301:Insect Hormones; D009842:Oligopeptides; D010446:Peptide Fragments; D010972:Platelet Activating Factor; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C064647:antiflammin P2; C031161:cecropin A