Lymphocyte adhesion to human endothelial cells induces tissue factor expression via a juxtacrine pathway.
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.
Schmid
E
E
Department of Pharmacological Research, Dr. Karl Thomae GmbH, Biberach/Riss, Germany.
Müller
T H
TH
Budzinski
R M
RM
Pfizenmaier
K
K
Binder
K
K
D001381:Azepines / Q000494:pharmacology; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics; D002450:Cell Communication; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D046508:Culture Techniques / Q000295:instrumentation; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000502:physiology*; D005786:Gene Expression Regulation; D006680:HLA Antigens / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008233:Lymphotoxin-alpha / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000502:physiology*; D013925:Thromboplastin / Q000096:biosynthesis* / Q000235:genetics; D014230:Triazoles / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics; D014471:Umbilical Veins
D001381:Azepines; D015815:Cell Adhesion Molecules; D017077:Culture Media, Conditioned; D019040:E-Selectin; D006680:HLA Antigens; D008070:Lipopolysaccharides; D008233:Lymphotoxin-alpha; D011994:Recombinant Proteins; D014230:Triazoles; D014409:Tumor Necrosis Factor-alpha; C052518:WEB 2086; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D013925:Thromboplastin