| First Author | Cambien B | Year | 2003 |
| Journal | J Clin Invest | Volume | 112 |
| Issue | 10 | Pages | 1589-96 |
| PubMed ID | 14617760 | Mgi Jnum | J:117987 |
| Mgi Id | MGI:3698327 | Doi | 10.1172/JCI19284 |
| Citation | Cambien B, et al. (2003) Antithrombotic activity of TNF-alpha. J Clin Invest 112(10):1589-96 |
| abstractText | 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. |
