Signaling by E-selectin and ICAM-1 induces endothelial tissue factor production via autocrine secretion of platelet-activating factor and tumor necrosis factor alpha.
Based on previous studies showed adhesion molecule-dependent induction of tissue factor upon endothelium-lymphocyte interactions, we investigated whether E-selectin and ICAM-1 are linked to signaling pathways leading to tissue factor gene expression. Cellular interaction was mimicked by antibody cross-linking of E-selectin and ICAM-1 on the surface of human umbilical vein endothelial cells (HUVECs), resulting in induction of tissue factor mRNA and protein expression. Tissue factor production could be independently abolished by antibodies against TNF-alpha and by WEB 2086, a platelet-activating factor (PAF) receptor antagonist. Because WEB 2086 prevented the production and/or secretion of TNF-alpha by HUVECs, these results provide evidence for E-selectin- and ICAM-1-linked signal pathways leading to tissue factor synthesis in endothelial cells via an autocrine feedback loop involving PAF and TNF-alpha secretion.
Department of Pharmacological Research, Dr. Karl Thomae GmbH, Biberach, Germany.
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E
Schmid
T H
TH
Müller
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RM
Budzinski
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K
Binder
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K
Pfizenmaier
D000937:Antigen-Antibody Reactions; D001381:Azepines / Q000494:pharmacology; D002478:Cells, Cultured; D019040:E-Selectin / Q000276:immunology / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000502:physiology*; D007371:Interferon-gamma / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000378:metabolism*; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D011994:Recombinant Proteins; D015398:Signal Transduction / Q000502:physiology*; D013268:Stimulation, Chemical; D013925:Thromboplastin / Q000096:biosynthesis*; D014230:Triazoles / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D001381:Azepines; D019040:E-Selectin; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D011994:Recombinant Proteins; D014230:Triazoles; D014409:Tumor Necrosis Factor-alpha; C039351:platelet activating factor receptor; C052518:WEB 2086; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D013925:Thromboplastin