期刊
BLOOD
卷 114, 期 2, 页码 425-436出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2008-03-145821
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资金
- Heart and Stroke Foundation of Canada (Ottawa, ON)
- Canadian Institutes of Health Research (CIHR)
- Canadian Blood Services
- St Michael's Hospital
- Canada Foundation for Innovation
- International Cooperation Research Fund of Anhui Provincial Scientific and Technologic Committee (China)
- Heart and Stroke Foundation of Ontario
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 gamma chain with beta 3 integrin was required for this process. Furthermore, Fg(-/-) platelets significantly increased P-selectin expression following transfusion into beta 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. (Blood. 2009; 114: 425-436)
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