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Blood, 15 February 2004, Vol. 103, No. 4, pp. 1342-1347. Prepublished online as a Blood First Edition Paper on October 23, 2003; DOI 10.1182/blood-2003-09-3051. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-09-3051v1 103/4/1342    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Pawlinski, R. Articles by Mackman, N. Search for Related Content PubMed PubMed Citation Articles by Pawlinski, R. Articles by Mackman, N. Related Collections Hemostasis, Thrombosis, and Vascular Biology Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Role of tissue factor and protease-activated receptors in a mouse model of endotoxemia Rafal Pawlinski, Brian Pedersen, Gernot Schabbauer, Michael Tencati, Todd Holscher, William Boisvert, Patricia Andrade-Gordon, Rolf Dario Frank, and Nigel Mackman From the Departments of Immunology and Cell Biology, The Scripps Research Institute, La Jolla, CA; and J & J Pharmaceutical Research & Development, Spring House, PA. Sepsis is associated with a systemic activation of coagulation and an excessive inflammatory response. Anticoagulants have been shown to inhibit both coagulation and inflammation in sepsis. In this study, we used both genetic and pharmacologic approaches to analyze the role of tissue factor and protease-activated receptors in coagulation and inflammation in a mouse endotoxemia model. We used mice expressing low levels of the procoagulant molecule, tissue factor (TF), to analyze the effects of TF deficiency either in all tissues or selectively in hematopoietic cells. Low TF mice had reduced coagulation, inflammation, and mortality compared with control mice. Similarly, a deficiency of TF expression by hematopoietic cells reduced lipopolysaccharide (LPS)–induced coagulation, inflammation, and mortality. Inhibition of the down-stream coagulation protease, thrombin, reduced fibrin deposition and prolonged survival without affecting inflammation. Deficiency of either protease activated receptor-1 (PAR-1) or protease activated receptor-2 (PAR-2) alone did not affect inflammation or survival. However, a combination of thrombin inhibition and PAR-2 deficiency reduced inflammation and mortality. These data demonstrate that hematopoietic cells are the major pathologic site of TF expression during endotoxemia and suggest that multiple protease-activated receptors mediate crosstalk between coagulation and inflammation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: N. Mackman The Role of Tissue Factor and Factor VIIa in Hemostasis Anesth. Analg., May 1, 2009; 108(5): 1447 - 1452. [Abstract] [Full Text] [PDF] F. Niessen, C. Furlan-Freguia, J. A. Fernandez, L. O. Mosnier, F. J. Castellino, H. Weiler, H. Rosen, J. H. Griffin, and W. Ruf Endogenous EPCR/aPC-PAR1 signaling prevents inflammation-induced vascular leakage and lethality Blood, March 19, 2009; 113(12): 2859 - 2866. [Abstract] [Full Text] [PDF] W. J. Sandberg, B. Halvorsen, A. Yndestad, C. Smith, K. Otterdal, F. R. Brosstad, S. S. 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