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Elucidation of mechanisms for macrophage-mediated xenograft refection and a novel approach to prevent macrophage-mediated xenograft rejection by gene introduction of human CD47 to xenogenic cells

Research Project

Project/Area Number 16591257
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionHIROSHIMA UNIVERSITY

Principal Investigator

OHDAN Hideki  Hiroshima University, Hospital, Research Associate, 病院, 助手 (10363061)

Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsXenotransplatation / Macrophage / Rejection / CD47 / Transgenics
Research Abstract

Xenotransplantation of pig organs to humans is a possible solution for the shortage of donor organs for transplantation. Although host macrophages are known to contribute at least in part to rapid clearance of transplanted xenogeneic cells, the mechanisms underlying macrophage-induced killing of xenogeneic cells has not been fully addressed. We here demonstrated that human reticulo-endothelial macrophages can phagocytose porcine cells in the absence of antibody or complement opsonization, and that the removal of α1,3-galactosyl xenoantigens from the porcine cells failed to prevent the phagocytosis. We also demonstrated that the interspecies incompatibility of CD47 significantly contributes to the phagocytosis of xenogeneic cells by macrophages. To further determine whether the expression of human CD47 on porcine cells could confer protection from phagocytosis by human macrophages, we generated human CD47-expressing porcine cell lines by transfecting the porcine B lymphoma-like cells with a human CD47 expressing plasmid. Human CD47 expression on porcine cells radically reduced the susceptibility of the cells to phagocytosis by human reticulo-endothelial macrophages, regardless of the presence or absence of antibody opsonization. These results indicate that the interspecies incompatibility of CD47 significantly contributes to the rejection of xenogeneic cells by macrophages. Genetic manipulation of porcine cells for expression of human CD47 may provide a novel approach in preventing macrophage-mediated xenograft rejection through inhibitory CD47-SIRPα signaling.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (4 results)

All 2005

All Journal Article (4 results)

  • [Journal Article] Antibody-and complement-independent phagocytotic and cytolytic activities of human macrophages toward porcine cells2005

    • Author(s)
      Kentaro Ida
    • Journal Title

      Xenotransplantation 12

      Pages: 181-188

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Antibody- and complement-independent phagocytotic and cytolytic activities of human macrophages toward porcine cells2005

    • Author(s)
      Kentaro Ide
    • Journal Title

      Xenotransplantation 12(3)

      Pages: 181-188

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Antibody- and complement-independent phagocytotic and cytolytic activities of human macrophages toward porcine cells2005

    • Author(s)
      Kentaro Ide
    • Journal Title

      Xenotransplantation 12・3

      Pages: 181-188

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Antibody- and complement-independent phagocytotic and cytolytic activities of human macrophages toward porcine cells2005

    • Author(s)
      Ide K, Ohdan H, et al.
    • Journal Title

      Xenotransplantation 12

      Pages: 181-188

    • Related Report
      2004 Annual Research Report

URL: 

Published: 2004-04-01   Modified: 2016-04-21  

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