title: Human CD47 expression permits survival of porcine cells in immunodeficient mice that express SIRPα capable of binding to human CD47.
abstract: Signal regulatory protein α (SIRPα) is a critical immune inhibitory receptor on macrophages, and its interaction with CD47 prevents autologous phagocytosis. We have previously shown that pig CD47 does not interact with human SIRPα, and that human CD47 expression inhibits  phagocytosis of porcine cells by human macrophages in vitro. In this study, we have investigated the potential of human CD47 expression to promote porcine cell survival in vivo. Human CD47-expressing and control porcine B-lymphoma cells were transplanted into T- and B-cell-deficient nonobese  diabetic/severe combined immunodeficient (NOD/SCID) mice that express SIRPα capable of interacting with human CD47. Only the human CD47-expressing porcine lymphoma cells survived and were able to form tumors in NOD/SCID mice; however, both the control and human CD47-expressing porcine  cells survived in macrophage-depleted NOD/SCID mice. These results indicate that transgenic expression of human CD47 may provide an effective approach to inhibiting macrophage-mediated xenograft rejection in clinical xenotransplantation.
authors.affiliation: College of Animal Science and Technology, Jilin Agricultural University, Changchun, China.
authors.forename: Chunfeng
authors.initials: C
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Kentaro
authors.initials: K
authors.lastname: Ide
authors.forename: Yuantao
authors.initials: Y
authors.lastname: Wang
authors.forename: Nico
authors.initials: N
authors.lastname: Van Rooijen
authors.forename: Hideki
authors.initials: H
authors.lastname: Ohdan
authors.forename: Yong-Guang
authors.initials: YG
authors.lastname: Yang
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D051928:CD47 Antigen / Q000235:genetics / Q000378:metabolism*; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D008264:Macrophages / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009369:Neoplasms / Q000473:pathology; D010587:Phagocytosis; D011485:Protein Binding; D011971:Receptors, Immunologic / Q000378:metabolism*; D013552:Swine; D014183:Transplantation, Heterologous
chemical_list: D051928:CD47 Antigen; C501922:Sirpa protein, mouse; D011971:Receptors, Immunologic