Complement Depletion Improves Human Red Blood Cell Reconstitution in Immunodeficient Mice

• Published in: Stem cell reports Vol. 9; no. 4; pp. 1034 - 1042
• Main Authors: Chen, Bing, Fan, Wei, Zou, Jun, Zhang, Siwen, He, Jin, Shu, Chang, Zhao, Guoqing, Sun, Tianmeng, Hu, Zheng, Yang, Yong-Guang
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10.10.2017; Elsevier
• Subjects: Animals; Biomarkers; Cell Adhesion - immunology; Cell Survival - immunology; complement; Complement Inactivating Agents - pharmacology; Complement System Proteins - immunology; Elapid Venoms - pharmacology; Erythrocytes - cytology; Erythrocytes - immunology; Erythrocytes - metabolism; erythropoiesis; Erythropoiesis - immunology; Graft Survival - drug effects; Graft Survival - immunology; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - immunology; Hematopoietic Stem Cells - metabolism; human; humanized mice; Humans; immunodeficient mice; Immunohistochemistry; in vivo; Macrophages - drug effects; Macrophages - immunology; Macrophages - metabolism; Mice, Inbred NOD; Mice, SCID; opsonization; phagocytes; Phagocytes - immunology; Phagocytes - metabolism; red blood cells; Transplantation, Heterologous; xenotransplantation; red blood cells; immunodeficient mice; phagocytes; humanized mice; opsonization; xenotransplantation; erythropoiesis; complement; human; in vivo
• ISSN: 2213-6711; 2213-6711
• DOI: 10.1016/j.stemcr.2017.08.018

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. •Both professional and non-professional phagocytes reject human RBC in mice•Complement mediates human RBC destruction by murine phagocytes•Phagocyte plus complement inhibition enhances human RBC reconstitution in mice In this article, Yang, Hu, and colleagues report a critical role for mouse complement in the rejection of human RBCs in immunodeficient mice. Complement depletion markedly improved human RBC reconstitution in macrophage-depleted mice, constituting a valuable pre-clinical model to examine human erythropoiesis and RBC function.