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血小板浓缩物的全面蛋白质组学研究:血小板蛋白质组、储存时间和 Mirasol 病原体减少技术。

A comprehensive proteomics study on platelet concentrates: Platelet proteome, storage time and Mirasol pathogen reduction technology.

机构信息

a Department of Blood Cell Research , Sanquin Research and Landsteiner Laboratory, Academic Medical Centre (AMC), University of Amsterdam (UvA) , Amsterdam , The Netherlands.

b Department of Hematology , Hospital Clínico San Carlos, Instituto de Investigación Sanitaria San Carlos (IdISSC) , Madrid , Spain.

出版信息

Platelets. 2019;30(3):368-379. doi: 10.1080/09537104.2018.1447658. Epub 2018 Mar 19.

Abstract

Platelet concentrates (PCs) represent a blood transfusion product with a major concern for safety as their storage temperature (20-24°C) allows bacterial growth, and their maximum storage time period (less than a week) precludes complete microbiological testing. Pathogen inactivation technologies (PITs) provide an additional layer of safety to the blood transfusion products from known and unknown pathogens such as bacteria, viruses, and parasites. In this context, PITs, such as Mirasol Pathogen Reduction Technology (PRT), have been developed and are implemented in many countries. However, several studies have shown in vitro that Mirasol PRT induces a certain level of platelet shape change, hyperactivation, basal degranulation, and increased oxidative damage during storage. It has been suggested that Mirasol PRT might accelerate what has been described as the platelet storage lesion (PSL), but supportive molecular signatures have not been obtained. We aimed at dissecting the influence of both variables, that is, Mirasol PRT and storage time, at the proteome level. We present comprehensive proteomics data analysis of Control PCs and PCs treated with Mirasol PRT at storage days 1, 2, 6, and 8. Our workflow was set to perform proteomics analysis using a gel-free and label-free quantification (LFQ) approach. Semi-quantification was based on LFQ signal intensities of identified proteins using MaxQuant/Perseus software platform. Data are available via ProteomeXchange with identifier PXD008119. We identified marginal differences between Mirasol PRT and Control PCs during storage. However, those significant changes at the proteome level were specifically related to the functional aspects previously described to affect platelets upon Mirasol PRT. In addition, the effect of Mirasol PRT on the platelet proteome appeared not to be exclusively due to an accelerated or enhanced PSL. In summary, semi-quantitative proteomics allows to discern between proteome changes due to Mirasol PRT or PSL, and proves to be a methodology suitable to phenotype platelets in an unbiased manner, in various physiological contexts.

摘要

血小板浓缩物 (PCs) 是一种输血产品,其储存温度(20-24°C)允许细菌生长,最大储存时间(不到一周)排除了完全的微生物检测,这引起了人们对其安全性的极大关注。病原体灭活技术 (PIT) 为输血产品提供了针对已知和未知病原体(如细菌、病毒和寄生虫)的额外安全层。在这种情况下,已经开发并在许多国家实施了病原体灭活技术,例如 Mirasol 病原体减少技术 (PRT)。然而,几项研究已经在体外表明,Mirasol PRT 在储存过程中会引起一定程度的血小板形状变化、过度激活、基础脱颗粒和氧化损伤增加。有人认为,Mirasol PRT 可能会加速所谓的血小板储存损伤(PSL),但尚未获得支持的分子特征。我们旨在从蛋白质组水平上剖析 Mirasol PRT 和储存时间这两个变量的影响。我们展示了对照 PCs 和用 Mirasol PRT 处理的 PCs 在储存第 1、2、6 和 8 天的蛋白质组全面分析数据。我们的工作流程设定为使用无胶和无标签定量 (LFQ) 方法进行蛋白质组学分析。半定量是基于 MaxQuant/Perseus 软件平台对鉴定蛋白的 LFQ 信号强度进行的。数据可通过 ProteomeXchange 以标识符 PXD008119 获得。我们在储存过程中发现 Mirasol PRT 和对照 PCs 之间存在微小差异。然而,在蛋白质组水平上的这些显著变化与之前描述的 Mirasol PRT 对血小板产生影响的功能方面有关。此外,Mirasol PRT 对血小板蛋白质组的影响似乎并非仅仅由于加速或增强了 PSL。总之,半定量蛋白质组学可以区分由于 Mirasol PRT 或 PSL 引起的蛋白质组变化,并被证明是一种适用于在各种生理情况下以无偏倚方式表型化血小板的方法。

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