Signaling by E-selectin and ICAM-1 Induces Endothelial Tissue Factor Production via Autocrine Secretion of Platelet-Activating Factor and Tumor Necrosis Factor α

Abstract

Based on previous studies showing adhesion molecule-dependent induction of tissue factor upon endotheliumlymphocyte 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-α and by WEB 2086, a platelet-activating factor (PAF) receptor antagonist. Because WEB 2086 prevented the production and/or secretion of TNF-α 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-α secretion.