Macrophages prevent human red blood cell reconstitution in immunodeficient mice
Macrophages prevent human red blood cell reconstitution in immunodeficient mice
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DOI：
10.1182/blood-2010-11-321414
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发表时间：
2011-11-24
期刊：
影响因子：
20.3
通讯作者：
Yang, Yong-Guang
中科院分区：
文献类型：
--
作者：
Hu, Zheng;Van Rooijen, Nico;Yang, Yong-Guang
支持人红细胞生成的动物模型对于评估人RBC在生理和疾病环境下的生物学功能以及评估体外RBC分化的方案将是非常有价值的。在此，我们分析了移植了人CD 34（+）胎肝细胞和胎儿胸腺组织的NOD/SCID或NOD/SCID/γ c（-/-）小鼠中的人RBC重建。尽管在骨髓中检测到大量人CD 45（-）CD 71（+）有核未成熟红系细胞，但在这些小鼠的血液中检测不到人RBC。巨噬细胞耗竭后，血液中可检测到人RBC，但停药后再次消失。此外，用人促红细胞生成素和IL-3治疗显著增加了巨噬细胞耗竭的人源化小鼠中的人RBC重建，但对照组没有。人RBC比CD 47缺陷型小鼠RBC显著更快的排斥表明，除了CD 47-SIRPa信号传导不足之外的机制参与小鼠中的人RBC异种排斥。所有考虑，我们的数据表明，人红细胞是非常容易被免疫缺陷小鼠的巨噬细胞排斥。因此，需要使用免疫缺陷小鼠作为体内模型来研究人红细胞生成和RBC功能，以防止巨噬细胞对人RBC的排斥反应。（血。2011;118（22）：5938-5946）
An animal model supporting human erythropoiesis will be highly valuable for assessing the biologic function of human RBCs under physiologic and disease settings, and for evaluating protocols of in vitro RBC differentiation. Herein, we analyzed human RBC reconstitution in NOD/SCID or NOD/SCID/gamma c(-/-) mice that were transplanted with human CD34(+) fetal liver cells and fetal thymic tissue. Although a large number of human CD45(-)CD71(+) nucleated immature erythroid cells were detected in the bone marrow, human RBCs were undetectable in the blood of these mice. Human RBCs became detectable in blood after macrophage depletion but disappeared again after withdrawal of treatment. Furthermore, treatment with human erythropoietin and IL-3 significantly increased human RBC reconstitution in macrophage-depleted, but not control, humanized mice. Significantly more rapid rejection of human RBCs than CD47-deficient mouse RBCs indicates that mechanisms other than insufficient CD47-SIRP alpha signaling are involved in human RBC xenorejection in mice. All considered, our data demonstrate that human RBCs are highly susceptible to rejection by macrophages in immunodeficient mice. Thus, strategies for preventing human RBC rejection by macrophages are required for using immunodeficient mice as an in vivo model to study human erythropoiesis and RBC function. (Blood. 2011;118(22):5938-5946)