Red blood cells with elevated cytoplasmic Ca2+ are primarily taken up by splenic marginal zone macrophages and CD207+dendritic cells
Red blood cells with elevated cytoplasmic Ca2+ are primarily taken up by splenic marginal zone macrophages and CD207+dendritic cells
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DOI：
10.1111/trf.13612
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发表时间：
2016-07-01
期刊：
影响因子：
2.9
通讯作者：
Oldenborg, Per-Arne
中科院分区：
文献类型：
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作者：
Larsson, Anders;Hult, Andreas;Oldenborg, Per-Arne
背景当红细胞储存在血库条件下时，正常红细胞（RBC）的寿命可能会显着缩短，导致输血后24小时存活率降低。储存的红细胞的损害可能是多因素的，因为储存的红细胞具有衰老和自杀性红细胞死亡（红斑狼疮）的共同特征。由于细胞内 Ca2+ 浓度 ([Ca2+](i)) 增加是红斑狼疮的一个关键特征，因此我们在此研究了储存的人类红细胞是否增加了 [Ca2+](i) 以及在小鼠模型中摄取此类红细胞背后的机制。 研究设计和方法使用 Ca2+ 探针 Fluo-3 和流式细胞术测定红细胞的细胞内 Ca2+ 含量。使用流式细胞术和免疫组织化学分析，在受体小鼠中研究了经 Ca2+ 离子载体处理的鼠红细胞 (Ca2+-RBC) 的体内摄取。结果在血库条件下储存长达 42 天期间，一小部分人红细胞积累了 [Ca2+](i)。在输注新鲜或Ca2+-RBC的小鼠模型中，输注后1小时内Ca2+-RBC主要被MARCO+脾边缘区巨噬细胞和CD11c+CD207+树突状细胞(DC)捕获。与此形成鲜明对比的是，新鲜输注的在循环中正常老化的红细胞被 F4/80+ 红髓巨噬细胞清除的速度要慢得多，并且优先被 F4/80+ 红髓巨噬细胞清除。 Ca2+-RBC 上的 CD47 不影响脾吞噬细胞对其的清除。 结论 小部分红细胞在储存过程中积累 [Ca2+](i)，在小鼠模型中，此类红细胞被脾巨噬细胞和 DC 识别，其识别方式与报道的有核凋亡细胞类似。
BACKGROUNDThe normal red blood cell (RBC) life span may be significantly reduced when RBCs are stored under blood bank conditions, resulting in a reduced 24-hour survival after transfusion. The damage of stored RBCs is probably multifactorial as stored RBCs share features of both senescence and suicidal RBC death (eryptosis). Since an increased intracellular Ca2+ concentration ([Ca2+](i)) is one key feature of eryptosis, we here investigated if stored human RBCs had increased [Ca2+](i) and the mechanisms behind uptake of such RBCs in a murine model.STUDY DESIGN AND METHODSThe intracellular Ca2+ content of RBCs was determined using the Ca2+ probe Fluo-3 and flow cytometry. In vivo uptake of Ca2+ ionophore-treated murine RBCs (Ca2+-RBCs) was investigated in recipient mice, using flow cytometry and immunohistochemical analysis.RESULTSA small fraction of human RBCs accumulated [Ca2+](i) during storage for up to 42 days under blood bank conditions. In a murine model, where fresh or Ca2+-RBCs were transfused, Ca2+-RBCs were mainly trapped by MARCO+ splenic marginal zone macrophages and CD11c+ CD207+ dendritic cells (DCs) within 1 hour after transfusion. In marked contrast, freshly transfused RBCs aging normally in circulation were cleared much slower and preferentially by F4/80+ red pulp macrophages. CD47 on the Ca2+-RBCs did not affect their clearance by splenic phagocytic cells.CONCLUSIONSA small fraction of RBCs accumulate [Ca2+](i) during storage, and in a murine model such RBCs are recognized by splenic macrophages and DCs in ways similar to what has been reported for nucleated apoptotic cells.