References
Query Results -- Details
MGI Accession ID: MGI:3698327
J Number: J:117987
Other Accession IDs:
Title: Antithrombotic activity of TNF-alpha.
Authors: Cambien B; Bergmeier W; Saffaripour S; Mitchell HA; Wagner DD
Journal: J Clin Invest
Volume: 112
Issue: 10
Date: 2003 Nov
Year: 2003
Pages: 1589-96
Review Status: Peer Reviewed
Abstract:
Basic and clinical observations suggest that thrombosis and inflammation are closely related. Here we addressed the role played by TNF-alpha in thrombus formation and growth in an in vivo mouse model. Using intravital microscopy, we show that systemic administration of TNF-alpha at doses found in sepsis transiently inhibits thrombus formation and delays arterial occlusion upon vascular injury. These results were reflected in a prolonged bleeding time. Platelets isolated from the TNF-alpha-treated mice showed a marked decrease in fibrinogen binding and P-selectin expression as well as reduced platelet aggregation in response to various agonists. In contrast, in vitro treatment of platelets with TNF-alpha did not affect their function. TNF receptor 1- and 2-deficient mice exhibited normal thrombogenesis in the presence of TNF-alpha. Additionally, the inhibitory effect of TNF-alpha was lost either after treatment with NG-monomethyl-l-arginine, an inhibitor of NO production, or in mice deficient for iNOS. These results indicate that under inflammatory conditions, when leukocytes need free passage to transmigrate into tissues, TNF-alpha decreases platelet activation and inhibits thrombi formation. This effect is not exerted directly on platelets but mediated through the rapid generation of NO in the vessel wall.
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