Metabolic reprogramming under hypoxic storage preserves faster oxygen unloading from stored red blood cells.
Metabolic reprogramming under hypoxic storage preserves faster oxygen unloading from stored red blood cells.
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DOI：
10.1182/bloodadvances.2022007774
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发表时间：
2022-09-27
期刊：
影响因子：
7.5
通讯作者：
Swietach, Pawel
中科院分区：
文献类型：
--
作者：
Rabcuka, Julija;Blonski, Slawomir;Meli, Athinoula;Sowemimo-Coker, Samuel;Zaremba, Damian;Stephenson, Daniel;Dzieciatkowska, Monika;Nerguizian, David;Cardigan, Rebecca;Korczyk, Piotr M.;Smethurst, Peter A.;D'Alessandro, Angelo;Swietach, Pawel
相对于标准血库方案，低氧储存通过代谢重塑保持更快的O2从红细胞卸载。氧气处理的功能评估证明了低氧储存对血液制品的质量和保质期的有益影响。储存的红细胞（RBC）会引起生化和形态学变化，统称为储存病变。在功能上，储存性病变表现为RBC的氧卸载较慢，这可能会损害输血的疗效，其中临床需要快速增加向组织的氧输送。最近对大量真实世界数据的分析将更长的储存时间与受体死亡率增加联系起来。用腺苷、肌苷和丙酮酸的制剂进行生化复壮可以恢复气体处理特性，但其实施对于大多数临床情况是不切实际的。我们测试了在缺氧下储存是否也保留了RBC的气体处理特性，缺氧以前显示出减缓生化降解。设计用于在充氧和缺氧灌流液之间快速切换的微流体室用于储存长达49天的样品的单细胞氧饱和度成像。还通过流式细胞术分析等分试样的侧向散射（O2卸载动力学的建议代理）、代谢组学、脂质组学和氧化还原蛋白质组学。对于基准测试，在标准储存4周时对单元进行生化再生。低氧储存加速了储存至35天的单位的O2卸载，这种效应与侧向散射相关，但与血红蛋白的翻译后修饰无关。虽然低氧储存和复壮产生不同的生化变化，包括丙酮酸，景天庚酮糖1-磷酸，和2/3磷酸-d-甘油酸的代谢产物的子集，是一个共同的签名，与O2卸载的变化。气体处理和脂质组学变化之间的相关性不大。因此，RBC的低氧储存保留了关键的代谢途径和O2交换特性，从而改善了血液制品的功能质量并可能影响输血结果。
Relative to standard blood-bank protocols, hypoxic storage preserves faster O2 unloading from red cells through metabolic remodelling. Functional appraisal of O2 handling demonstrates a beneficial effect of hypoxic storage on the quality and shelf life of blood products. Stored red blood cells (RBCs) incur biochemical and morphological changes, collectively termed the storage lesion. Functionally, the storage lesion manifests as slower oxygen unloading from RBCs, which may compromise the efficacy of transfusions where the clinical imperative is to rapidly boost oxygen delivery to tissues. Recent analysis of large real-world data linked longer storage with increased recipient mortality. Biochemical rejuvenation with a formulation of adenosine, inosine, and pyruvate can restore gas-handling properties, but its implementation is impractical for most clinical scenarios. We tested whether storage under hypoxia, previously shown to slow biochemical degradation, also preserves gas-handling properties of RBCs. A microfluidic chamber, designed to rapidly switch between oxygenated and anoxic superfusates, was used for single-cell oxygen saturation imaging on samples stored for up to 49 days. Aliquots were also analyzed flow cytometrically for side-scatter (a proposed proxy of O2 unloading kinetics), metabolomics, lipidomics, and redox proteomics. For benchmarking, units were biochemically rejuvenated at 4 weeks of standard storage. Hypoxic storage hastened O2 unloading in units stored to 35 days, an effect that correlated with side-scatter but was not linked to posttranslational modifications of hemoglobin. Although hypoxic storage and rejuvenation produced distinct biochemical changes, a subset of metabolites including pyruvate, sedoheptulose 1-phosphate, and 2/3 phospho-d-glycerate, was a common signature that correlated with changes in O2 unloading. Correlations between gas handling and lipidomic changes were modest. Thus, hypoxic storage of RBCs preserves key metabolic pathways and O2 exchange properties, thereby improving the functional quality of blood products and potentially influencing transfusion outcomes.
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影响因子：
10.1
作者：
D'Alessandro A;Fu X;Kanias T;Reisz JA;Culp-Hill R;Guo Y;Gladwin MT;Page G;Kleinman S;Lanteri M;Stone M;Busch MP;Zimring JC;Recipient Epidemiology and Donor Evaluation Study-III (REDS III)
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Recipient Epidemiology and Donor Evaluation Study-III (REDS III)
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影响因子：
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Johansson, Par Ingemar
影响因子：
8
作者：
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通讯作者：
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影响因子：
2.9
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D'Alessandro, Angelo;Culp-Hill, Rachel;Cristman, A. M.
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Cristman, A. M.
影响因子：
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