Sickle Cell Trait Increases Red Blood Cell Storage Hemolysis and Post-Transfusion Clearance in Mice
Sickle Cell Trait Increases Red Blood Cell Storage Hemolysis and Post-Transfusion Clearance in Mice
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DOI：
10.1016/j.ebiom.2016.08.006
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发表时间：
2016-09-01
期刊：
影响因子：
11.1
通讯作者：
Gladwin, Mark T.
中科院分区：
文献类型：
--
作者：
Osei-Hwedieh, David O.;Kanias, Tamir;Gladwin, Mark T.
背景资料：在批准的储存时间限制下输血与输血后红细胞（RBC）回收率较低和溶血相关，这会增加血浆无细胞血红蛋白和铁，从而诱导内皮功能障碍并损害宿主防御。有注意到的变化，在固有的储存变化率和红细胞输血后恢复的捐助者之间的差异，但调节这一过程的遗传决定因素尚不清楚。我们使用来自人源化转基因镰状细胞半合子小鼠的血液在同种异体和异种输血的小鼠模型中探索RBC储存稳定性和输血后恢复（Hba（tm 1 Paz）Hbb（tm 1 Tow）Tg（HBA-HBBs）41 Paz/J）和具有共同基因突变镰状细胞性状（HbAS）的人供体。储存的HbAS RBC的快速输血后清除与巨噬细胞介导的摄取或血管内溶血无关，而是通过脾、肾和肝中增强的隔离。HbAS RBC本质上不同于HbAA RBC，随着细胞在冷藏中老化，膜变形性降低，导致输注的HbAS RBC通过截留在器官微循环中而加速清除。解释：常见的遗传变异HbAS增强RBC储存功能障碍，并在批准的储存限制下对HbAS RBC的使用提出了挑衅性问题。(C)2016作者由爱思唯尔公司出版
Background: Transfusion of blood at the limits of approved storage time is associated with lower red blood cell (RBC) post-transfusion recovery and hemolysis, which increases plasma cell-free hemoglobin and iron, proposed to induce endothelial dysfunction and impair host defense. There is noted variability among donors in the intrinsic rate of storage changes and RBC post-transfusion recovery, yet genetic determinants that modulate this process are unclear.Methods: We explore RBC storage stability and post-transfusion recovery in murine models of allogeneic and xenogeneic transfusion using blood from humanized transgenic sickle cell hemizygous mice (Hba(tm1Paz)Hbb(tm1Tow)Tg( HBA-HBBs)41Paz/J) and human donors with a common genetic mutation sickle cell trait (HbAS).Findings: Human and transgenic HbAS RBCs demonstrate accelerated storage time-dependent hemolysis and reduced post-transfusion recovery in mice. The rapid post-transfusion clearance of stored HbAS RBC is unrelated to macrophage-mediated uptake or intravascular hemolysis, but by enhanced sequestration in the spleen, kidney and liver. HbAS RBCs are intrinsically different from HbAA RBCs, with reduced membrane deformability as cells age in cold storage, leading to accelerated clearance of transfused HbAS RBCs by entrapment in organ microcirculation.Interpretation: The common genetic variant HbAS enhances RBC storage dysfunction and raises provocative questions about the use of HbAS RBCs at the limits of approved storage. (C) 2016 The Authors. Published by Elsevier B.V.