储存红细胞中酸性鞘磷脂酶的抑制可减少输血相关的肺部炎症。
Acid Sphingomyelinase Inhibition in Stored Erythrocytes Reduces Transfusion-Associated Lung Inflammation.
作者信息
Hoehn Richard S, Jernigan Peter L, Japtok Lukasz, Chang Alex L, Midura Emily F, Caldwell Charles C, Kleuser Burkhard, Lentsch Alex B, Edwards Michael J, Gulbins Erich, Pritts Timothy A
机构信息
*Department of Surgery and Institute for Military Medicine, University of Cincinnati, Cincinnati, OH †Department of Toxicology, Institute of Nutritional Science, University of Potsdam, Germany ‡Department of Molecular Biology, University of Duisburg-Essen, Essen, Germany.
出版信息
Ann Surg. 2017 Jan;265(1):218-226. doi: 10.1097/SLA.0000000000001648.
OBJECTIVE
We aimed to identify the role of the enzyme acid sphingomyelinase in the aging of stored units of packed red blood cells (pRBCs) and subsequent lung inflammation after transfusion.
SUMMARY BACKGROUND DATA
Large volume pRBC transfusions are associated with multiple adverse clinical sequelae, including lung inflammation. Microparticles are formed in stored pRBCs over time and have been shown to contribute to lung inflammation after transfusion.
METHODS
Human and murine pRBCs were stored with or without amitriptyline, a functional inhibitor of acid sphingomyelinase, or obtained from acid sphingomyelinase-deficient mice, and lung inflammation was studied in mice receiving transfusions of pRBCs and microparticles isolated from these units.
RESULTS
Acid sphingomyelinase activity in pRBCs was associated with the formation of ceramide and the release of microparticles. Treatment of pRBCs with amitriptyline inhibited acid sphingomyelinase activity, ceramide accumulation, and microparticle production during pRBC storage. Transfusion of aged pRBCs or microparticles isolated from aged blood into mice caused lung inflammation. This was attenuated after transfusion of pRBCs treated with amitriptyline or from acid sphingomyelinase-deficient mice.
CONCLUSIONS
Acid sphingomyelinase inhibition in stored pRBCs offers a novel mechanism for improving the quality of stored blood.
目的
我们旨在确定酸性鞘磷脂酶在浓缩红细胞（pRBCs）储存单元老化及输血后肺部炎症中的作用。
总结背景数据
大量输注pRBCs与多种不良临床后果相关，包括肺部炎症。随着时间的推移，储存的pRBCs中会形成微粒，并且已证明这些微粒会导致输血后肺部炎症。
方法
将人和小鼠的pRBCs与酸性鞘磷脂酶的功能性抑制剂阿米替林一起或不与阿米替林一起储存，或者从酸性鞘磷脂酶缺陷小鼠中获取pRBCs，然后在接受从这些单元中分离出的pRBCs和微粒输血的小鼠中研究肺部炎症。
结果
pRBCs中的酸性鞘磷脂酶活性与神经酰胺的形成和微粒的释放有关。用阿米替林处理pRBCs可抑制pRBCs储存期间的酸性鞘磷脂酶活性、神经酰胺积累和微粒产生。将老化的pRBCs或从老化血液中分离出的微粒输注到小鼠体内会引起肺部炎症。在用阿米替林处理的pRBCs或来自酸性鞘磷脂酶缺陷小鼠输注后，这种炎症会减轻。
结论
抑制储存的pRBCs中的酸性鞘磷脂酶为提高储存血液的质量提供了一种新机制。
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