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Blood, 15 January 2009, Vol. 113, No. 3, pp. 714-722. Prepublished online as a Blood First Edition Paper on October 29, 2008; DOI 10.1182/blood-2008-02-137901. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-02-137901v1 113/3/714    most recent Alert me when this article is cited Alert me if a correction is posted 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 Shibamiya, A. Articles by Kanse, S. M Search for Related Content PubMed PubMed Citation Articles by Shibamiya, A. Articles by Kanse, S. M Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 5, 2008 Accepted August 20, 2008 A key role for toll-like receptor-3 (TLR3) in disrupting the hemostasis balance on endothelial cells Aya Shibamiya, Karin Hersemeyer, Thomas Schmidt Woll, Daniel Sedding, Jan-Marcus Daniel, Stefan Bauer, Takatoshi Koyama, Klaus T Preissner, and Sandip M Kanse* Institute of Biochemistry, Justus-Liebig-University, Giessen, Germany Institute of Immunology, Philipps University, Marburg, Germany Graduate School of Health Sciences, Tokyo Medical and Dental University, Tokyo, Japan * Corresponding author; email: sandip.kanse{at}biochemie.med.uni-giessen.de. Various virus infections cause dysfunctional hemostasis and in some instances lead to the development of viral hemorrhagic fever syndrome. How do diverse viruses induce the expression of tissue factor on vascular cells? We hypothesize that a direct stimulation of pattern recognition receptors (PRR) by viral nucleic acids may be the key. dsRNA is produced by many viruses and is recognized by various PRR, including Toll like receptor-3 (TLR3). We have investigated whether poly I:C, a model for viral double stranded RNA (dsRNA), can influence cellular hemostasis. Poly I:C could up-regulate tissue factor and down-regulate thrombomodulin expression on endothelial cells but not on monocytes. The response to poly I:C was diminished upon siRNA-mediated inhibition of TLR3, but not other PRR. In vivo, application of poly I:C induced similar changes in the aortic endothelium of mice as determined by enface microscopy. D-dimer, a circulating marker for enhanced coagulation and fibrinolysis, and tissue fibrin deposition was elevated. All the hemostasis-related responses to poly I:C, but not cytokine secretion, were blunted in TLR3-/- mice. Hence, the activation of TLR3 can induce the pro-coagulant state in the endothelium and this could be relevant for understanding the mechanisms of viral stimulation of hemostasis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Hagele, R. Allam, R. D. Pawar, and H.-J. Anders Double-stranded RNA activates type I interferon secretion in glomerular endothelial cells via retinoic acid-inducible gene (RIG)-1 Nephrol. Dial. Transplant., November 1, 2009; 24(11): 3312 - 3318. [Abstract] [Full Text] [PDF]

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