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Blood, 9 July 2009, Vol. 114, No. 2, pp. 425-436. Prepublished online as a Blood First Edition Paper on March 30, 2009; DOI 10.1182/blood-2008-03-145821. This Article Full Text (PDF) All Versions of this Article: blood-2008-03-145821v1 114/2/425    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 Yang, H. Articles by Ni, H. Search for Related Content PubMed PubMed Citation Articles by Yang, H. Articles by Ni, H. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 17, 2008 Accepted March 17, 2009 Fibrinogen is required for maintenance of platelet intracellular and cell surface P-selectin expression Hong Yang, Sean Lang, Zhimin Zhai, Ling Li, Walter H.A. Kahr, Pingguo Chen, Jelena Brkic, Christopher M. Spring, Matthew J. Flick, Jay L. Degen, John Freedman, and Heyu Ni* Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada Department of Biological Sciences, University of Toronto at Scarborough, Toronto, Ontario, Canada The Center Laboratory of Anhui Provincial Hospital, the Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China Program in Cell Biology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada Department of Paediatrics, Division of Haematology/Oncology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada Canadian Blood Services, Toronto, Ontario, Canada Toronto Platelet Immunobiology Group and Department of Laboratory Medicine, Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada Children's Hospital Research Foundation and University of Cincinnati, Cincinnati, OH, United States Department of Medicine, University of Toronto, Toronto, Ontario, Canada Department of Physiology, University of Toronto, Toronto, Ontario, Canada * Corresponding author; email: nih{at}smh.toronto.on.ca. Platelet P-selectin plays important roles in inflammation and contributes to thrombosis and hemostasis. While it has been reported that von Willebrand factor (VWF) affects P-selectin expression on endothelial cells, little information is available regarding regulation of platelet P-selectin expression. Here, we first observed that P-selectin expression was significantly decreased on platelets of fibrinogen and VWF double deficient mice. Subsequently, we identified this was due to fibrinogen deficiency. Impaired P-selectin expression on fibrinogen-deficient platelets was further confirmed in human hypofibrinogenemic patients. We demonstrated that this impairment is unlikely due to excessive P-selectin shedding, deficient fibrinogen-mediated cell surface P-selectin binding, or impaired platelet granule release, but rather is due to decreased platelet P-selectin content. Fibrinogen transfusion completely recovered this impairment in fibrinogen-deficient (Fg-/-) mice, and engagement of the C-terminus of the fibrinogen chain with 3 integrin was required for this process. Furthermore, Fg-/- platelets significantly increased P-selectin expression following transfusion into 3 integrin-deficient mice and when cultured with fibrinogen. These data suggest fibrinogen may play important roles in inflammation, thrombosis and hemostasis via enhancement of platelet P-selectin expression. Since human fibrinogen levels vary significantly in normal and diseased populations, P-selectin as an activation marker on platelets should be used with caution. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Fibrinogen selects selectins Hansjörg Schwertz, Guy A. Zimmerman, and Andrew S. Weyrich Blood 2009 114: 234. [Full Text] [PDF] This article has been cited by other articles: H. Schwertz, G. A. Zimmerman, and A. S. Weyrich Fibrinogen selects selectins Blood, July 9, 2009; 114(2): 234 - 234. [Full Text] [PDF]

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