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.