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Blood, 17 September 2009, Vol. 114, No. 12, pp. 2521-2529. Prepublished online as a Blood First Edition Paper on July 20, 2009; DOI 10.1182/blood-2009-02-205914. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2009-02-205914v1 114/12/2521    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Google Scholar Articles by Song, D. Articles by Liu, S. F. PubMed PubMed Citation Articles by Song, D. Articles by Liu, S. F. Related Collections Thrombosis and Hemostasis Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  THROMBOSIS AND HEMOSTASIS Activation of endothelial intrinsic NF-B pathway impairs protein C anticoagulation mechanism and promotes coagulation in endotoxemic mice Dongmei Song1,*, Xiaobing Ye1,*, Honglei Xu1, and Shu Fang Liu1 1 Centers for Heart and Lung Research, and Immunology and Inflammation, Feinstein Institute for Medical Research and Division of Pulmonary and Critical Care Medicine, Long Island Jewish Medical Center, New Hyde Park, NY Although the role of systemic activation of the nuclear factor B (NF-B) pathway in septic coagulation has been well documented, little is known about the contribution of endothelial-specific NF-B signaling in this pathologic process. Here, we used transgenic mice that conditionally overexpress a mutant I-B, an inhibitor of NF-B, selectively on endothelium, and their wild-type littermates to define the role of endothelial-specific NF-B in septic coagulation. In wild-type mice, lipopolysaccharide (LPS) challenge (5 mg/kg intraperitoneally) caused markedly increased plasma markers of coagulation, decreased plasma fibrinogen level, and widespread tissue fibrin deposition, which were abrogated by endothelial NF-B blockade in transgenic mice. Endothelial NF-B blockade inhibited tissue factor expression in endothelial cells, but not in leukocytes. Endothelial NF-B blockade did not inhibit LPS-induced tissue factor expression in heart, kidney, and liver. Endothelial NF-B blockade prevented LPS down-regulation of endothelial protein C receptor (EPCR) and thrombomodulin protein expressions, inhibited tissue tumor necrosis factor- converting enzyme activity, reduced EPCR shedding, and restored plasma protein C level. Our data demonstrate that endothelial intrinsic NF-B signaling plays a pivotal role in septic coagulation and suggests a link between endothelial-specific NF-B activation and the impairment of the thrombomodulin-protein C-EPCR anticoagulation pathway. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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