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Blood, 1 July 2006, Vol. 108, No. 1, pp. 167-176. Prepublished online as a Blood First Edition Paper on March 2, 2006; DOI 10.1182/blood-2005-08-3219. This Article Full Text (PDF) All Versions of this Article: 2005-08-3219v1 108/1/167    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 Stahl, A.-l. Articles by Karpman, D. Search for Related Content PubMed PubMed Citation Articles by Stahl, A.-l. Articles by Karpman, D. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 10, 2005 Accepted February 22, 2006 Lipopolysaccharide from enterohemorrhagic Escherichia coli binds to platelets via TLR4 and CD62 and is detected on circulating platelets in patients with hemolytic uremic syndrome Anne-lie Stahl, Majlis Svensson, Matthias Morgelin, Catharina Svanborg, Phillip I Tarr, Jody C Mooney, Sandra L Watkins, Roger Johnson, and Diana Karpman* Department of Pediatrics, Clinical Sciences Lund, Lund University, Lund, Sweden Institute of Laboratory Medicine, Section for Microbiology, Immunology and Glycobiology, Lund University, Lund, Sweden Department of Clinical and Experimental Infectious Medicine, Lund University, Lund, Sweden Division of Pediatric Gastroenterology and Nutrition, Washington University School of Medicine, Saint Louis, MO, USA Children's Hospital and Regional Medical Center, Seattle, WA, USA Children's Hospital and Regional Medical Center, Seattle, WA, USA; Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, USA The Public Health Agency of Canada, Laboratory for Foodborne Zoonoses, Guelph, Canada * Corresponding author; email: diana.karpman{at}med.lu.se. This study presents evidence that human platelets bind lipopolysaccharide (LPS) from enterohemorrhagic Escherichia coli (EHEC) via a complex of toll-like receptor 4 (TLR4) and CD62, leading to their activation. TLR4 colocalized with CD62 on the platelet membrane, and the TLR4 specificity of LPS binding to platelets was confirmed using C57BL/10ScN mice lacking tlr4. Only platelets from TLR4 wild-type mice bound O157LPS in vitro. After in vivo injection, O157LPS bound to platelets from wild-type mice, which exhibited reduced platelet counts compared to mice lacking TLR4. Mouse experiments confirmed that O157LPS binding to TLR4 is the primary event leading to platelet activation, as shown by expression of CD40L, and that CD62 further contributes to this process. Activation of human platelets by EHEC-LPS was demonstrated by expression of the activated GPIIb/IIIa receptor, CD40L and fibrinogen binding. In perfusion experiments platelet activation on endothelial cells was TLR4- and CD62-dependent. O157LPS was detected on platelets from 12/14 children with EHEC-associated hemolytic uremic syndrome (HUS) as well as on platelets from two children before development of HUS but not on platelets from EHEC-infected children that did not develop HUS (n=3). These data suggest that O157LPS on platelets might contribute to platelet consumption in HUS. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A.-l. Stahl, F. Vaziri-Sani, S. Heinen, A.-C. Kristoffersson, K.-H. Gydell, R. Raafat, A. Gutierrez, O. Beringer, P. F. Zipfel, and D. Karpman Factor H dysfunction in patients with atypical hemolytic uremic syndrome contributes to complement deposition on platelets and their activation Blood, June 1, 2008; 111(11): 5307 - 5315. [Abstract] [Full Text] [PDF] J. Villagra, S. Shiva, L. A. Hunter, R. F. Machado, M. T. 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