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Blood, 15 January 2007, Vol. 109, No. 2, pp. 836-842. Prepublished online as a Blood First Edition Paper on September 28, 2006; DOI 10.1182/blood-2006-04-019794. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2006-04-019794v1 109/2/836    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wang, H. Articles by Yang, Y.-G. Search for Related Content PubMed PubMed Citation Articles by Wang, H. Articles by Yang, Y.-G. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 26, 2006 Accepted August 12, 2006 Attenuation of phagocytosis of xenogeneic cells by manipulating CD47 Hui Wang, Jon VerHalen, Maria Lucia Madariaga, Shuanglin Xiang, Shumei Wang, Ping Lan, Per-Arne Oldenborg, Megan Sykes, and Yong-Guang Yang* Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA Beth Israel Deaconess Medical Center of Harvard Medical School, Boston, MA Section for Histology and Cell Biology, Umea University, Umea, Sweden * Corresponding author; email: yongguang.yang{at}tbrc.mgh.harvard.edu. Signal regulatory protein (SIRP) is a critical immune inhibitory receptor on macrophages, and its interaction with CD47, a ligand for SIRP, 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. Similar to CD47-/- mouse cells, porcine RBCs failed to induce SIRP tyrosine phosphorylation in mouse macrophages. Blocking SIRP with anti- mouse SIRP 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 to 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 SIRP may provide a novel approach to prevent phagocyte-mediated xenograft rejection. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. S. Isenberg, D. D. Roberts, and W. A. Frazier CD47: A New Target in Cardiovascular Therapy Arterioscler Thromb Vasc Biol, April 1, 2008; 28(4): 615 - 621. [Abstract] [Full Text] [PDF] W. Y. Lee, D. A. Weber, O. Laur, E. A. Severson, I. McCall, R. P. Jen, A. C. Chin, T. Wu, K. M. Gernet, and C. A. Parkos Novel Structural Determinants on SIRP{alpha} that Mediate Binding to CD47 J. Immunol., December 1, 2007; 179(11): 7741 - 7750. [Abstract] [Full Text] [PDF] H. Wang, M. L. Madariaga, S. Wang, N. Van Rooijen, P.-A. Oldenborg, and Y.-G. Yang Lack of CD47 on nonhematopoietic cells induces split macrophage tolerance to CD47null cells PNAS, August 21, 2007; 104(34): 13744 - 13749. [Abstract] [Full Text] [PDF] K. Ide, H. Wang, H. Tahara, J. Liu, X. Wang, T. Asahara, M. Sykes, Y.-G. Yang, and H. Ohdan Role for CD47-SIRP{alpha} signaling in xenograft rejection by macrophages PNAS, March 20, 2007; 104(12): 5062 - 5066. [Abstract] [Full Text] [PDF]

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