Puget Sound Blood Center Research Institute, Seattle, Washington; Department of Pathology and Laboratory Medicine, Center for Transfusion and Cellular Therapies, Department of Pediatrics, Aflac Cancer and Blood Disorders Center, Emory University School of Medicine, Atlanta, Georgia; Metabolon, Inc., Research Triangle Park, North Carolina; Laboratory of Transfusion Biology, Department of Pathology and Cell Biology, Columbia University Medical Center-New York Presbyterian Hospital, New York, New York; Department of Medicine, University of Washington, Seattle, Washington.
Transfusion. 2014 Jan;54(1):137-48. doi: 10.1111/trf.12264. Epub 2013 May 30.
Red blood cell (RBC) transfusion is a lifesaving therapy, the logistic implementation of which requires RBC storage. However, stored RBCs exhibit substantial donor variability in multiple characteristics, including hemolysis in vitro and RBC recovery in vivo. The basis of donor variability is poorly understood.
We applied a murine model of RBC storage and transfusion to test the hypothesis that genetically distinct inbred strains of mice would demonstrate strain-specific differences in RBC storage. In vivo recoveries were determined by monitoring transfused RBCs over 24 hours. Timed aliquots of stored RBCs were subjected to tandem chromatography/mass spectrometry analysis to elucidate metabolic changes in the RBCs during storage.
Using independent inbred mouse strains as donors, we found substantial strain-specific differences in posttransfusion RBC recovery in vivo after standardized refrigerated storage in vitro. Poor posttransfusion RBC recovery correlated with reproducible metabolic variations in the stored RBC units, including increased lipid peroxidation, decreased levels of multiple natural antioxidants, and accumulation of cytidine. Strain-dependent differences were also observed in eicosanoid generation (i.e., prostaglandins and leukotrienes).
These findings provide the first evidence of strain-specific metabolomic differences after refrigerated storage of murine RBCs. They also provide the first definitive biochemical evidence for strain-specific variation of eicosanoid generation during RBC storage. The molecules described that correlate with RBC storage quality, and their associated biochemical pathways, suggest multiple causal hypotheses that can be tested regarding predicting the quality of RBC units before transfusion and developing methods of improved RBC storage.
红细胞（RBC）输血是一种救生疗法，其物流实施需要 RBC 储存。然而，储存的 RBC 在多个特性上表现出大量供体变异性，包括体外溶血和体内 RBC 恢复。供体变异性的基础知之甚少。
我们应用 RBC 储存和输血的小鼠模型来检验以下假设，即遗传上不同的近交系小鼠将表现出 RBC 储存方面的特定于品系的差异。通过在 24 小时内监测输注的 RBC 来确定体内恢复情况。储存的 RBC 定时等分试样进行串联色谱/质谱分析，以阐明 RBC 在储存过程中的代谢变化。
使用独立的近交系小鼠作为供体，我们发现经过标准化冷藏体外储存后，体内输注后 RBC 的恢复存在显著的品系特异性差异。输注后 RBC 恢复不良与储存 RBC 单位中可重复的代谢变化相关，包括脂质过氧化增加、多种天然抗氧化剂水平降低以及胞苷积累。在类二十烷酸（即前列腺素和白三烯）的生成中也观察到了依赖于品系的差异。
这些发现提供了冷藏储存的小鼠 RBC 后品系特异性代谢组差异的第一个证据。它们还首次提供了冷藏储存过程中 RBC 中类二十烷酸生成的品系特异性变异的明确生化证据。与 RBC 储存质量相关的分子及其相关生化途径表明了多个因果假说，可以对输血前 RBC 单位的质量进行预测，并开发改进 RBC 储存的方法进行检验。
