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Blood, 1 October 2005, Vol. 106, No. 7, pp. 2417-2423. Prepublished online as a Blood First Edition Paper on June 16, 2005; DOI 10.1182/blood-2005-03-0916. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-03-0916v1 106/7/2417    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 Andonegui, G. Articles by Kubes, P. Search for Related Content PubMed PubMed Citation Articles by Andonegui, G. Articles by Kubes, P. Related Collections Hemostasis, Thrombosis, and Vascular Biology Immunobiology Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Platelets express functional Toll-like receptor-4 Graciela Andonegui, Steven M. Kerfoot, Kelly McNagny, Kirsten V. J. Ebbert, Kamala D. Patel, and Paul Kubes From the Immunology Research Group, Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Calgary, AB, Canada; and the Biomedical Research Centre, University of British Columbia, Vancouver, BC, Canada. Profound thrombocytopenia occurs in humans with sepsis and in mice administered lipopolysaccharide (LPS). Growing evidence indicates that platelets may contribute to these abnormalities, but whether that is a direct result of LPS activation of platelets or an indirect result of other inflammatory mechanisms remains unclear. Here we demonstrate that although platelets do not increase P-selectin expression in response to LPS, platelets bind more avidly to fibrinogen under flow conditions in a Toll-like receptor-4 (TLR4)-dependent manner. In addition, we find that CD41+ megakaryocytes grown from fetal livers and adult circulating platelets express significant amounts of TLR4. LPS induced thrombocytopenia in wild-type mice but not in TLR4-deficient (TLR4def) mice. Wild-type platelets accumulated in the lungs of wild-type mice in response to LPS; TLR4def platelets did not. However, wild-type platelets did not accumulate in the lungs of LPS-treated TLR4def mice. Neutrophils also accumulated in the lungs, and this preceded platelet accumulation. Neutrophil depletion completely abolished LPS-induced platelet sequestration into the lungs, but platelet depletion did not affect neutrophil accumulation. Thus, our data show for the first time that platelets do express functional levels of TLR4, which contribute to thrombocytopenia through neutrophil-dependent pulmonary sequestration in response to LPS. (Blood. 2005;106:2417-2423) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Zhou, G. Andonegui, C. H. Y. Wong, and P. Kubes Role of Endothelial TLR4 for Neutrophil Recruitment into Central Nervous System Microvessels in Systemic Inflammation J. Immunol., October 15, 2009; 183(8): 5244 - 5250. [Abstract] [Full Text] [PDF] M. Delvaeye and E. M. Conway Coagulation and innate immune responses: can we view them separately? Blood, September 17, 2009; 114(12): 2367 - 2374. [Abstract] [Full Text] [PDF] G. Zhang, J. Han, E. J. Welch, R. D. Ye, T. A. Voyno-Yasenetskaya, A. B. Malik, X. Du, and Z. 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