Complement Depletion Improves Human Red Blood Cell Reconstitution in Immunodeficient Mice

• Main Authors: Bing Chen, Wei Fan, Jun Zou, Siwen Zhang, Jin He, Chang Shu, Guoqing Zhao, Tianmeng Sun, Zheng Hu, Yong-Guang Yang
• Format: Article
• Language: English
• Published: Elsevier 2017-10-01
• Series: Stem Cell Reports
• Subjects: red blood cells; erythropoiesis; complement; phagocytes; in vivo; human; immunodeficient mice; humanized mice; opsonization; xenotransplantation
• Online Access: http://www.sciencedirect.com/science/article/pii/S2213671117303752

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.