Platelets regulate vascular endothelial stability: assessing the storage lesion and donor variability of apheresis platelets.
Platelets regulate vascular endothelial stability: assessing the storage lesion and donor variability of apheresis platelets.
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作者：
Baimukanova G;Miyazawa B;Potter DR;Muench MO;Bruhn R;Gibb SL;Spinella PC;Cap AP;Cohen MJ;Pati S
在目前的血库实践中，血小板（PLT）在22°C下储存在血浆中，轻轻搅拌长达5天。迄今为止，储存和供体变异性对PLT调节血管完整性的影响尚不清楚。在这项研究中，我们检查了供体的白细胞减少的新鲜（第1天）或储存（第5天）的血小板对血管内皮屏障功能在体外和体内的变异性。在体外，通过分析跨内皮电阻（TEER）来评估PLT对内皮细胞（EC）单层通透性的影响。通过阻抗聚集测定法分析PLT聚集（止血潜力的量度）。在体内，在血管内皮生长因子A（VEGF-A）诱导的NSG小鼠血管通透性模型中研究PLT，并通过流式细胞术测量PLT循环。用新鲜的第1天PLT处理内皮单层导致EC屏障阻力增加，并以剂量依赖性方式降低渗透性。随后用第5天PLT处理EC单层显示血管保护作用减弱。在所有血小板功能指标中均观察到供体变异性。第1天PLT供体对TEER的影响比第5天PLT更多变。在小鼠中，尽管所有PLT（无论储存时间如何）均显示出对VEGF-A诱导的血管渗漏的显著保护，但与第1天PLT相比，第5天PLT显示出降低的保护。第1天的PLT在体内表现出针对VEGF-A攻击的血管渗漏的显著供体变异性。第1天PLT的全身循环水平高于第5天PLT。在体外和体内，第1天PLT在血管内皮渗透性测量中具有保护作用。供体变异性在第1天PLT中最为突出。在22°C下储存第1天和第5天之间的PLT单位时发现保护作用降低，从而表明第5天PLT减弱血管内皮渗透性的能力降低。
In current blood banking practices, platelets (PLTs) are stored in plasma at 22°C, with gentle agitation for up to 5 days. To date, the effects of storage and donor variability on PLT regulation of vascular integrity are not known. In this study, we examined the donor variability of leukoreduced fresh (Day 1) or stored (Day 5) PLTs on vascular endothelial barrier function in vitro and in vivo. In vitro, PLT effects on endothelial cell (EC) monolayer permeability were assessed by analyzing transendothelial electrical resistances (TEER). PLT aggregation, a measure of hemostatic potential, was analyzed by impedance aggregometry. In vivo, PLTs were investigated in a vascular endothelial growth factor A (VEGF-A)-induced vascular permeability model in NSG mice, and PLT circulation was measured by flow cytometry. Treatment of endothelial monolayers with fresh Day 1 PLTs resulted in an increase in EC barrier resistance and decreased permeability in a dose-dependent manner. Subsequent treatment of EC monolayers with Day 5 PLTs demonstrated diminished vasculoprotective effects. Donor variability was noted in all measures of PLT function. Day 1 PLT donors were more variable in their effects on TEER than Day 5 PLTs. In mice, while all PLTs regardless of storage time demonstrated significant protection against VEGF-A–induced vascular leakage, Day 5 PLTs exhibited reduced protection when compared to Day 1 PLTs. Day 1 PLTs demonstrated significant donor variability against VEGF-A–challenged vascular leakage in vivo. Systemic circulating levels of Day 1 PLTs were higher than those of Day 5 PLTs In vitro and in vivo, Day 1 PLTs are protective in measures of vascular endothelial permeability. Donor variability is most prominent in Day 1 PLTs. A decrease in the protective effects is found with storage of the PLT units between Day 1 and Day 5 at 22°C, thereby suggesting that Day 5 PLTs are diminished in their ability to attenuate vascular endothelial permeability.
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影响因子：
10.8
作者：
Bates DO
通讯作者：
Bates DO
DOI：
10.1097/ta.0b013e318227edbb
发表时间：
2011-08-01
影响因子：
--
作者：
Holcomb, John B.;Zarzabal, Lee A.;Wade, Charles E.
通讯作者：
Wade, Charles E.
影响因子：
2.9
作者：
Glenister, Kristen M.;Payne, Katherine A.;Sparrow, Rosemary L.
通讯作者：
Sparrow, Rosemary L.
DOI：
10.1182/blood.v35.4.549.549
发表时间：
1970-01-01
期刊：
BLOOD-THE JOURNAL OF HEMATOLOGY
影响因子：
--
作者：
MURPHY, S;SAYAR, SN;GARDNER, FH
通讯作者：
GARDNER, FH
DOI：
10.1097/ta.0b013e31823bdbf9
发表时间：
2011-12-01
影响因子：
--
作者：
Inaba, Kenji;Branco, Bernardino C.;Demetriades, Demetrios
通讯作者：
Demetriades, Demetrios