Year-end Sale % OFF 
Abstract
SummaryWe 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.
Highlights
As one of the most plentiful cell types in body, the red blood cell (RBC) is indispensable in oxygen and carbon dioxide transport (Goodnough et al, 2000)
We show that elimination of murine complement by cobra venom factor (CVF) nearly completely abrogated the adherence of human red blood cells (hRBCs) to murine phagocytic cells in vitro and that CVF significantly prolonged the survival of infused hRBCs in macrophage-depleted mice
But Not Human, Sera Promote the Adherence of Human RBCs to Murine Phagocytic Cells Because adherence to phagocytic cells is a significant event in the phagocytosis of target cells, we first assessed the potential of mouse sera to induce adherence of hRBCs to murine phagocytic cells
Summary
As one of the most plentiful cell types in body, the red blood cell (RBC) is indispensable in oxygen and carbon dioxide transport (Goodnough et al, 2000). The recent development of effective gene editing strategies, such as CRISPR/Cas technology (Suzuki et al, 2016), has increased the potential of curing these hematological disorders through transplantation of patient HSCs with the genetic errors corrected (Rees et al, 2010; Sankaran and Weiss, 2015). These studies have been hampered by the lack of a suitable animal model that permits in vivo assessment of human erythroid differentiation from adult HSCs or induced pluripotent stem cell (iPSC)derived HSCs and RBC function (Sankaran and Weiss, 2015). The low levels of hRBCs in human HSC-grafted mice that have been depleted of macrophages imply that other macrophageindependent mechanisms are involved, necessitating optimization of humanized mice with stable and high levels of hRBC chimerism in blood (Rahmig et al, 2016; Rongvaux et al, 2013)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
