Complement Depletion Improves Human Red Blood Cell Reconstitution in Immunodeficient Mice
Complement Depletion Improves Human Red Blood Cell Reconstitution in Immunodeficient Mice
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补体消耗改善免疫缺陷小鼠的人红细胞重建
DOI：
10.1016/j.stemcr.2017.08.018
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发表时间：
2017-10-10
影响因子：
5.9
通讯作者：
Yang, Yong-Guang
中科院分区：
文献类型：
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作者：
Chen, Bing;Fan, Wei;Yang, Yong-Guang
我们先前已经表明，人红细胞（hRBC）受到免疫缺陷小鼠巨噬细胞的强烈排斥。在这项研究中，我们发现小鼠血清诱导hRBC粘附到小鼠吞噬细胞，包括专职吞噬巨噬细胞和中性粒细胞以及非专职吞噬内皮细胞。补体被认为是负责小鼠血清诱导的hRBC粘附小鼠吞噬细胞。虽然在NOD/SCID小鼠中，通过眼镜蛇毒因子（CVF）进行补体耗竭，hRBC存活率没有改善，但CVF显著延长了通过氯膦酸盐脂质体耗竭吞噬巨噬细胞的小鼠中hRBC的存活率。这种联合治疗还协同改善了人CD 34（+）细胞移植小鼠中的hRBC重建，为检查人红细胞生成和RBC功能提供了有价值的模型。这些数据表明，补体可能是巨噬细胞对hRBC排斥反应的抑制剂，在其他类型的鼠吞噬细胞（如嗜中性粒细胞和内皮细胞）对hRBC的排斥反应中至关重要。
We have previously shown that human red blood cells (hRBCs) are subject to robust rejection by macrophages in immunodeficient mice. In this study, we found that mouse serum induces hRBC adherence to murine phagocytic cells, including professional phagocytic macrophages and neutrophils and non-professional phagocytic endothelial cells. Complement was found to be responsible for mouse-serum-induced hRBC adherence to murine phagocytic cells. Although hRBC survival was not improved in NOD/SCID mice with complement depletion by cobra venom factor (CVF), CVF significantly prolonged hRBC survival in mice that were depleted of phagocytic macrophages by clodronate-liposomes. This combination treatment also synergistically improved hRBC reconstitution in human CD34(+) cell-grafted mice, offering a valuable model to examine human erythropoiesis and RBC function. These data indicate that complement, which might be dispensable for hRBC rejection by macrophages, is critical in hRBC rejection by other types of murine phagocytic cells, such as neutrophils and endothelial cells.