文章基本信息

标题：β 3 phosphorylation of platelet α IIb β 3 is crucial for stability of arterial thrombus and microparticle formation in vivo
本地全文：下载
作者：Weiyi Feng ; Manojkumar Valiyaveettil ; Tejasvi Dudiki 等
期刊名称：Thrombosis Journal
印刷版ISSN：1477-9560
电子版ISSN：1477-9560
出版年度：2017
卷号：15
期号：1
页码：22
DOI：10.1186/s12959-017-0145-1
语种：English
出版社：BioMed Central
摘要：Background It is well accepted that functional activity of platelet integrin α_IIbβ₃ is crucial for hemostasis and thrombosis. The β₃ subunit of the complex undergoes tyrosine phosphorylation shown to be critical for outside-in integrin signaling and platelet clot retraction ex vivo. However, the role of this important signaling event in other aspects of prothrombotic platelet function is unknown. Method Here, we assess the role of β₃ tyrosine phosphorylation in platelet function regulation with a knock-in mouse strain, where two β₃ cytoplasmic tyrosines are mutated to phenylalanine (DiYF). We employed platelet transfusion technique and intravital microscopy for observing the cellular events involved in specific steps of thrombus growth to investigate in detail the role of β₃ tyrosine phosphorylation in arterial thrombosis in vivo . Results Upon injury, DiYF mice exhibited delayed arterial occlusion and unstable thrombus formation. The mean thrombus volume in DiYF mice formed on collagen was only 50% of that in WT. This effect was attributed to DiYF platelets but not to other blood cells and endothelium, which also carry these mutations. Transfusion of isolated DiYF but not WT platelets into irradiated WT mice resulted in reversal of the thrombotic phenotype and significantly prolonged blood vessel occlusion times. DiYF platelets exhibited reduced adhesion to collagen under in vitro shear conditions compared to WT platelets. Decreased platelet microparticle release after activation, both in vitro and in vivo, were observed in DiYF mice compared to WT mice. Conclusion β₃ tyrosine phosphorylation of platelet α_IIbβ₃ regulates both platelet pro-thrombotic activity and the formation of a stable platelet thrombus, as well as arterial microparticle release.
关键词：β 3 integrin phosphorylation ; Outside-in integrin signaling ; Microparticles ; Arterial thrombosis