Attenuation of phagocytosis of xenogeneic cells by manipulating CD47

作者：Wang Hui; VerHalen Jon; Madariaga Maria Lucia; Xiang Shuanglin; Wang Shumei; Lan Ping; Oldenborg Per Arne; Sykes Megan; Yang Yong Guang^*

来源：Blood, 2007, 109(2): 836-842.

DOI：10.1182/blood-2006-04-019794

Signal regulatory protein alpha (SIRP alpha) is a critical immune inhibitory receptor on macrophages, and its interaction with CD47, a ligand for SIRP alpha, prevents autologous phagocytosis. We hypothesized that interspecies incompatibility of CD47 may contribute to the rejection of xenogeneic cells by macrophages. Here, we show that pig CD47 does not interact with mouse SIPR alpha. Similar to CD47(-/-) mouse cells, porcine red blood cells (RBCs) failed to induce SIRP alpha tyrosine phosphorylation in mouse macrophages. Blocking SIRP alpha with antimouse SIRP alpha mAb (P84) significantly enhanced the phagocytosis of CD47(+/+) mouse cells, but did not affect the engulfment of porcine or CD47(-/-) mouse cells by mouse macrophages. CD47-deficient mice, whose macrophages do not phagocytose CD47(-/-) mouse cells, showed markedly delayed clearance of porcine RBCs compared with wild-type mouse recipients. Furthermore, mouse CD47 expression on porcine cells markedly reduced their phagocytosis by mouse macrophages both in vitro and in vivo. These results indicate that interspecies incompatibility of CD47 contributes significantly to phagocytosis of xenogeneic cells by macrophages and suggest that genetic manipulation of donor CD47 to improve its interaction with the recipient SIRPa may provide a novel approach to prevent phagocyte-mediated xenograft rejection.

• 出版日期2007-1-15
• 单位温州医科大学