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Title: The lectin-like domain of thrombomodulin confers protection from neutrophil-mediated tissue damage by suppressing adhesion molecule expression via nuclear factor kappaB and mitogen-activated protein kinase pathways
Authors: Conway, Edward ×
Van de Wouwer, Marlies Lutgart Julien
Pollefeyt, Saskia
Jurk, Kerstin
Van Aken, Hugo
De Vriese, Astrid
Weitz, Jeffrey I
Weiler, Hartmut
Hellings, Peter
Schaeffer, Paul
Herbert, Jean-Marc
Collen, Desire
Theilmeier, Gregor #
Issue Date: Sep-2002
Series Title: Journal of Experimental Medicine vol:196 issue:5 pages:565-77
Abstract: Thrombomodulin (TM) is a vascular endothelial cell (EC) receptor that is a cofactor for thrombin-mediated activation of the anticoagulant protein C. The extracellular NH(2)-terminal domain of TM has homology to C-type lectins that are involved in immune regulation. Using transgenic mice that lack this structure (TM(LeD/LeD)), we show that the lectin-like domain of TM interferes with polymorphonuclear leukocyte (PMN) adhesion to ECs by intercellular adhesion molecule 1-dependent and -independent pathways through the suppression of extracellular signal-regulated kinase (ERK)(1/2) activation. TM(LeD/LeD) mice have reduced survival after endotoxin exposure, accumulate more PMNs in their lungs, and develop larger infarcts after myocardial ischemia/reperfusion. The recombinant lectin-like domain of TM suppresses PMN adhesion to ECs, diminishes cytokine-induced increase in nuclear factor kappaB and activation of ERK(1/2), and rescues ECs from serum starvation, findings that may explain why plasma levels of soluble TM are inversely correlated with cardiovascular disease. These data suggest that TM has antiinflammatory properties in addition to its role in coagulation and fibrinolysis.
ISSN: 0022-1007
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular and Vascular Biology
Research Group Experimental Oto-rhino-laryngology
Laboratory for Pharmaceutical Biology (-)
Laboratory of Clinical Immunology
× corresponding author
# (joint) last author

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