Refrigeration-Induced Binding of von Willebrand Factor Facilitates Fast Clearance of Refrigerated Platelets.
Refrigeration-Induced Binding of von Willebrand Factor Facilitates Fast Clearance of Refrigerated Platelets.
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DOI：
10.1161/atvbaha.117.310062
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发表时间：
2017-12
期刊：
影响因子：
--
通讯作者：
Li R
中科院分区：
文献类型：
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作者：
Chen W;Druzak SA;Wang Y;Josephson CD;Hoffmeister KM;Ware J;Li R
用于输血治疗的单采血小板目前储存在室温下，因为冷藏后血小板在输血时迅速清除。在这项研究中，血管性血友病因子（VWF）在冷冻血小板的清除中的作用得到解决。将人和鼠血小板在透气袋中在4°C下冷藏24小时。测量了VWF结合、血小板信号传导事件以及输血后血小板恢复和存活率。冷藏后血浆VWF与血小板的结合急剧增加，证实了早期的研究。这种结合被特异性结合血小板糖蛋白（GP）Ibα的肽OS 1阻断，并且在VWF−/−血浆中不存在。尽管冷冻后GPIbα的表面表达减少，但在生理剪切下冷冻诱导的VWF结合诱导血小板上GPIbα机械感觉结构域展开，如其中线性表位暴露增加所证明的。冷冻和剪切处理也诱导了细胞内Ca 2+、磷脂酰丝氨酸暴露和血小板去唾液酸化的小幅升高，这些在VWF−/−血小板中不存在或被OS 1抑制。此外，冷藏的VWF-/-血小板显示出比野生型血小板更高的输血后恢复率和存活率。类似地，在冷藏期间向仅表达人GPIbα的转基因小鼠血小板中加入OS 1改善了它们的输血后恢复和存活。冷冻诱导的VWF与血小板的结合通过诱导GPIbα介导的信号传导促进血小板的快速清除。我们的研究结果表明，抑制VWF-GPIb α相互作用可能是一种潜在的策略，使血小板的冷冻输血治疗。
Apheresis platelets for transfusion treatment are currently stored at room temperature because after refrigeration platelets are rapidly cleared upon transfusion. In this study, the role of von Willebrand factor (VWF) in the clearance of refrigerated platelets is addressed. Human and murine platelets were refrigerated in gas-permeable bags at 4°C for 24 hours. VWF binding, platelet signaling events, and platelet post-transfusion recovery and survival were measured. After refrigeration the binding of plasma VWF to platelets was drastically increased, confirming earlier studies. The binding was blocked by peptide OS1 that bound specifically to platelet glycoprotein (GP)Ibα and was absent in VWF−/− plasma. Although surface expression of GPIbα was reduced after refrigeration, refrigeration-induced VWF binding under physiological shear induced unfolding of the GPIbα mechanosensory domain on the platelet, as evidenced by increased exposure of a linear epitope therein. Refrigeration and shear treatment also induced small elevation of intracellular Ca2+, phosphatidylserine exposure and desialylation of platelets, which were absent in VWF−/− platelets or inhibited by OS1. Furthermore, refrigerated VWF−/− platelets displayed increased post-transfusion recovery and survival than wild-type ones. Similarly, adding OS1 to transgenic murine platelets expressing only human GPIbα during refrigeration improved their post-transfusion recovery and survival. Refrigeration-induced binding of VWF to platelets facilitates their rapid clearance by inducing GPIbα-mediated signaling. Our results suggest that inhibition of the VWF-GPIbα interaction may be a potential strategy to enable refrigeration of platelets for transfusion treatment.