CD40L-CD40 interactions regulate endothelial cell surface tissue factor and thrombomodulin expression.
During immune responses, activated endothelial cells down-regulate thrombomodulin and up-regulate tissue factor expression leading to the development of a procoagulant surface. CD4+ T cells are known to promote endothelial cell procoagulant activity, however, the molecular interactions that mediate this effect are not completely known. CD40L is an activation-induced CD4+ T cell surface molecule that functionally interacts with CD40 expressed on endothelial cells. In this study we ask if CD40L-CD40 interactions modulate endothelial cell surface tissue factor or thrombomodulin expression in vitro. Human umbilical vein endothelial cells (HUVEC) were cocultured with control cells or CD40L+ Jurkat T cells in the presence or absence of anti-CD40L mAb. By two-color FACS analysis we demonstrated that CD40 ligation induces HUVEC tissue factor expression and thrombomodulin down-regulation. Utilizing neutralizing antibodies, we show that CD40L-mediated tissue factor and thrombomodulin modulation, as well as E-selectin and VCAM-1 upregulation, is independent of tumor necrosis factor alpha, interleukin-1alpha, or interleukin-1beta production. Together these data suggest that CD40L-CD40 interactions may directly regulate endothelial cell procoagulant activity during inflammatory responses.
Miller
D L
DL
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Yaron
R
R
Yellin
M J
MJ
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D019013:CD40 Antigens / Q000502:physiology*; D023201:CD40 Ligand; D002462:Cell Membrane / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis / Q000276:immunology; D019169:Jurkat Cells; D008562:Membrane Glycoproteins / Q000502:physiology*; D018180:Thrombomodulin / Q000096:biosynthesis*; D013925:Thromboplastin / Q000096:biosynthesis*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology; D014471:Umbilical Veins
D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D007375:Interleukin-1; D008562:Membrane Glycoproteins; D018180:Thrombomodulin; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand; D013925:Thromboplastin