HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Involvement of a CD47-dependent pathway in platelet adhesion on inflamed vascular endothelium under flow
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چکیده
Resting platelet adhesion to inflammatory vascular endothelium is thought to play a causal role in secondary thrombus formation or microcirculatory disturbance after vessel occlusion. However, though adhesion receptors involved in plateletmatrix interactions have been extensively studied, the molecular mechanisms involved in platelet-endothelium interactions are incompletely characterized and have been mainly studied under static conditions. Using human platelets or platelets from wild-type and CD47 / mice in whole blood, we demonstrated that at low shear rate, CD47 expressed on human and mouse platelets significantly contributes to platelet adhesion on tumor necrosis factor(TNF)–stimulated vascular endothelial cells. Using the CD47 agonist peptide 4N1K and blocking monoclonal antibodies (mAbs), we showed that CD47 binds the cell-binding domain (CBD) of endothelial thrombospondin-1 (TSP-1), inducing activation of the platelet IIb 3 integrin that in turn becomes able to link the endothelial receptors intercellular adhesion molecule 1 (ICAM-1) and v 3. Platelet CD36 and GPIb are also involved because platelet incubation with blocking mAbs directed against each of these 2 receptors significantly decreased platelet arrest. Given that anti-CD47 treatment of platelets did not further decrease the adhesion of anti-CD36–treated platelets and CD36 is a TSP-1 receptor, it appears that CD36/TSP-1 interaction could trigger the CD47-dependent pathway. Overall, CD47 antagonists may be potentially useful to inhibit platelet adhesion on inflamed endothelium. (Blood. 2003;101: 4836-4843)
منابع مشابه
INVOLVEMENT OF A CD47-DEPENDENT PATHWAY IN PLATELET ADHESION ON INFLAMED VASCULAR ENDOTHELIUM UNDER FLOW running title: CD47 and platelet adhesion on inflamed endothelium
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تاریخ انتشار 2003