Macrophages prevent human red blood cell reconstitution in immunodeficient mice

Institute of Immunology, Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, China.
Blood (Impact Factor: 10.45). 09/2011; 118(22):5938-46. DOI: 10.1182/blood-2010-11-321414
Source: PubMed


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/γc(-/-) 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-SIRPα 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.

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Available from: Nico Van Rooijen, Dec 14, 2013
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    • "We therefore sought to optimize the mouse model used to assess human erythrocyte transfusion. Earlier reports of erythrocyte transfusion into NOG mice suggested the efficacy of using infused PB- RBCs as a decoy (Giarratana et al., 2005, 2011; Jiménez- Díaz et al., 2009) or injecting clodronate-liposomes to deplete macrophages in vivo (Arnold et al., 2011; Hu et al., 2011). We therefore tested the effect of clodronateliposomes on imERYPC circulation in mice pretreated with decoy RBCs. "
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