LYMPHOCYTE ADHESION TO HUMAN ENDOTHELIAL-CELLS INDUCES TISSUE FACTOR EXPRESSION VIA A JUXTACRINE PATHWAY

To study the effect of lymphocyte adhesion on the procoagulant activit y of endothelial cells, we have stimulated HUVECs with interferon-gamm a to upregulate adhesion molecules. Subsequent addition of lymphocytes induced the expression of tissue factor (TF) by HUVECs. Both CD4(+) a nd CD8(+) T-cells promoted this TF synthesis via distinct adhesion mol ecules (CD4(+) T-cells: E-selectin and ICAM-I; CD8(+) T-cells: MHC-I m olecules). In addition, tumor necrosis factor-alpha and -beta (TNF alp ha, TNF beta) and platelet-activating factor (PAF) were involved in ly mphocyte-mediated TF expression on HUVECs. We demonstrate that PAF pla ys a pivotal role in this process. Adhesion of lymphocytes to endothel ial cell surface molecules induced the release of PAF. PAF, in turn, c aused the production of TNF alpha and TNF beta, both of which are pote nt stimulators of TF expression.