The effects of 22째C and 4째C storage of platelets on vascular endothelial integrity and function
The effects of 22째C and 4째C storage of platelets on vascular endothelial integrity and function
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DOI：
10.1111/trf.13455
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发表时间：
2016-03-01
期刊：
影响因子：
2.9
通讯作者：
Pati, Shibani
中科院分区：
文献类型：
--
作者：
Baimukanova, Gyulnar;Miyazawa, Byron;Pati, Shibani
尽管迄今为止对血小板（PLT）储存进行的大多数研究都集中在PLT止血功能上，但4 ℃ PLT对内皮屏障通透性调节的影响仍然未知。在这项研究中，我们比较了室温（22摄氏度）储存和（4摄氏度）储存的血小板调节血管内皮细胞（EC）的渗透性在体外和体内的影响。研究设计和方法第1天，第5天，第7天leukoreducedapheresis血小板储存在4或22摄氏度进行了研究，在体外和体内。在体外，血小板对EC的渗透性和屏障功能，粘附和阻抗聚集法的影响进行了研究。在体内，使用血管渗漏的小鼠模型，测量血管渗漏的衰减和循环PLT数。用第5天或第7天的PLT对EC单层进行MTT处理，在22 ℃和4 ℃下储存，平均导致EC渗透性的类似降低。然而，个体样本的分析揭示了供体依赖性的显著变化。额外的体外测量显示，在4 ℃储存的情况下，随着时间的推移，炎症介质、非特异性PLT-内皮聚集和TRAP、ASPI、ADP和胶原蛋白的聚集损失减少。在小鼠中，虽然22 ℃和4 ℃ PLT均表现出对血管内皮生长因子A（VEGF-A）诱导的血管渗漏的显著保护，但22 ℃ PLT与4 ℃ PLT相比表现出增加的保护。与22 ℃ PLT相比，4 ℃ PLT的全身循环水平降低。结论在体外，4 ℃储存的PLT比22 ℃储存的PLT表现出更大的抑制EC渗透性的能力。在体内，22 ℃的PLT提供了对VEGF-A诱导的血管渗漏的上级控制。这种差异可能是由于体循环中4 ℃ PLT的清除率增加所致。
BACKGROUNDAlthough a majority of the studies conducted to date on platelet (PLT) storage have been focused on PLT hemostatic function, the effects of 4 degrees C PLTs on regulation of endothelial barrier permeability are still not known. In this study, we compared the effects of room temperature (22 degrees C) stored and (4 degrees C) stored PLTs on the regulation of vascular endothelial cell (EC) permeability in vitro and in vivo.STUDY DESIGN AND METHODSDay 1, Day 5, and Day 7 leukoreduced apheresis PLTs stored at 4 or 22 degrees C were studied in vitro and in vivo. In vitro, PLT effects on EC permeability and barrier function, adhesion, and impedance aggregometry were investigated. In vivo, using a mouse model of vascular leak, attenuation of vascular leak and circulating PLT numbers were measured.RESULTSTreatment of EC monolayers with Day 5 or Day 7 PLTs, stored at both 22 degrees C and 4 degrees C, resulted in similar decreases in EC permeability on average. However, analysis of individual samples revealed significant variation that was donor dependent. Additional in vitro measurements revealed a decrease in inflammatory mediators, nonspecific PLT-endothelial aggregation and attenuated loss of aggregation over time to TRAP, ASPI, ADP, and collagen with 4 degrees C storage. In mice, while 22 degrees C and 4 degrees C PLTs both demonstrated significant protection against vascular endothelial growth factor A (VEGF-A)-induced vascular leak 22 degrees C PLTs exhibited increased protection compared to 4 degrees C PLTs. Systemic circulating levels of 4 degrees C PLTs were decreased compared to 22 degrees C PLTs.CONCLUSIONSIn vitro, 4 degrees C-stored PLTs exhibit a greater capacity to inhibit EC permeability than 22 degrees C-stored PLTs. In vivo, 22 degrees C PLTs provide superior control of vascular leak induced by VEGF-A. This discrepancy may be due to increased clearance of 4 degrees C PLTs from the systemic circulation.