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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.
PLATELETS AND THROMBOPOIESIS Fibrinogen is required for maintenance of platelet intracellular and cell-surface P-selectin expression 31 Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON; 2 Canadian Blood Services, Toronto, ON; 3 Toronto Platelet Immunobiology Group and Department of Laboratory Medicine, Keenan Research Centre, Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, ON; 4 Department of Biological Sciences, University of Toronto at Scarborough, Toronto, ON; 5 The Center Laboratory of Anhui Provincial Hospital, The Second Affiliated Hospital of Anhui Medical University, Anhui, China; 6 Program in Cell Biology and 7 Department of Paediatrics, Division of Haematology/Oncology, The Hospital for Sick Children, University of Toronto, Toronto, ON; 8 Children's Hospital Research Foundation and University of Cincinnati, OH; Departments of 9 Medicine, and 10 Physiology, University of Toronto, Toronto, ON
Platelet P-selectin plays important roles in inflammation and contributes to thrombosis and hemostasis. Although 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
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| Copyright © 2009 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
chain with β3 integrin was required for this process. Furthermore, Fg–/– platelets significantly increased P-selectin expression following transfusion into β3 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. 
