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AbbreviationsCD47cluster of differentiation 47Ctcycle thresholdF2Afoot‐and‐mouth disease 2A peptideGAPDHglyceraldehyde‐3‐phosphate dehydrogenaseSEMstandard error of the meansiRNAsmall interfering RNASIRP‐αsignal‐regulatory protein alphaTFPItissue factor pathway inhibitorTSP‐1thrombospondin 1IntroductionAcute rejection is primarily initiated by binding of non‐Gal antibodies to the endothelium of pigs. Macrophages also play an important role in acute rejection, and rejection by macrophages in xenotransplantation has not yet been completely overcome. To overcome macrophage‐mediated immune responses in xenotransplantation, CD47 is a potent candidate that prevents phagocytosis by binding to macrophage surface protein signaling protein alpha (SIRP‐α). It has been reported that human CD47 (hCD47)‐expressing pig cells have a higher survival rate against phagocytosis in human macrophages than non‐expressing cells. Although hCD47 has a powerful effect that helps to overcome acute immune rejection by macrophages in xenotransplantation, the CD47 effect alone is not sufficient to resolve macrophage‐mediated acute rejection. Thus, to overcome macrophage‐mediated acute rejection, it is necessary to amplify the hCD47 effect in macrophages. However, when CD47 did not bind to SIRP‐a but it bound to another ligand thrombospondin‐1 (TSP‐1), CD47 failed to bind to SIRP‐a and failed to initiate suppression of phagocyte function, eventually inducing phagocytosis of erythrocytes and apoptosis of cells. In addition, when CD47 on target cells bound to SIRP‐a on macrophages,
Xenotransplantation – Wiley
Published: May 1, 2017
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