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
| Project/Area Number |
16591257
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
OHDAN Hideki Hiroshima University, Hospital, Research Associate, 病院, 助手 (10363061)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| 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)
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| Keywords | Xenotransplatation / Macrophage / Rejection / CD47 / Transgenics |
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| 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.
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Report
(3 results)
Research Products
(4 results)
