Abstract
Modulation of procoagulant and fibrinolytic properties of endothelial cells mediated by adhesion with activated T lymphocytes was studied by focusing on the CD40-CD40 Ligand (CD40L) interaction. Cultured human umbilical vein endothelial cells (HUVECs) were treated with interferon-γ to increase the expression of CD40, and co-cultured with T lymphocytes that had been isolated from peripheral blood, activated with PMA and ionomycin to induce the expression of CD40L and fixed with 1% paraformaldehyde. This co-culture gave rise to the generation of tissue factor (TF) on the surface of HUVECs, but co-culture of the HUVECs with non-activated T lymphocytes failed to do so. TF expressed on the HUVECs was specifically but only partially inhibited by an anti-CD40L monoclonal antibody. By contrast, co-culture of HUVECs with the activated and fixed T lymphocytes resulted in both down-regulation of thrombomodulin in HUVECs and decrease of release of tissue factor pathway inhibitor from HUVECs. Futhermore, the co-culture enhanced the release of tissue-type plasminogen activator (t-PA) from the HUVECs without affecting the release of plasminogen activator inhibitor-1, which was still in great excess of t-PA. These results altogether suggest that the CD40-CD40L-involved adhesion of activated T lymphocytes to endothelial cells that could occur at the inflammatory sites is likely to shift the nature of endothelial cell surface toward the thrombogenic state.
