Lymphocyte Adhesion to Human Endothelial Cells Induces Tissue Factor Expression via a Juxtacrine Pathway

Abstract

To study the effect of lymphocyte adhesion on the procoagulant activity of endothelial cells, we have stimulated HUVECs with interferon-gamma to upregulate adhesion molecules. Subsequent addition of lymphocytes induced the expression of tissue factor (TF) by HUVECs. Both CD4+ and CD8+ T-cells promoted this TF synthesis via distinct adhesion molecules (CD4+ T-cells: E-selectin and ICAM-1; CD8+ T-cells: MHC-I molecules). In addition, tumor necrosis factor-alpha and -beta (TNF alpha, TNF beta) and platelet-activating factor (PAF) were involved in lymphocyte-mediated TF expression on HUVECs. We demonstrate that PAF plays a pivotal role in this process. Adhesion of lymphocytes to endothelial cell surface molecules induced the release of PAF. PAF, in turn, caused the production of TNF alpha and TNF beta, both of which are potent stimulators of TF expression.