1999 Fiscal Year Final Research Report Summary
Analysis of the molecular mechanism of DXR and the therapeutic method
| Project/Area Number |
10470245
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Kyoto Prefectural University of Medicine |
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Principal Investigator |
NAKAJIMA Hiroo Kyoto Prefectural Univ. of Med. Dept. of Surgery II, Assistant Professor, 医学部, 助手 (70275212)
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| Project Period (FY) |
1998 – 1999
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| Keywords | Xenotransplantation / Apoptosis / Fas-Ligand / Bcl-2 / ADCC / NK cell / DXR |
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| Research Abstract |
In order to investigate the molecular mechanism of delayed xenograft rejection (DXR), and to look for its therapeutic means, we have used pig cell line (PK15) as target cells and human NK cells as effector cells, and performed the molecular analyses. (Results/Conclusion) ; In the presence of human serum, unprimed human PBL caused both the membrane and DNA-damages, implying that NK-cell dependent ADCC mechanism operates in this pig-to-human DXR. The expression of human FasL or mouse Bcl-2 molecules on the PK15 were able to partially inhibit the DNA damage. Although we have tried to introduce these molecules into in vivo ginea pig heart using vector techniques, sufficient expression of these molecules in hearts were not obtained, and the xenotransplantation of these hearts to LEW rats did not show the significant prolongation of the grafts survival as compared to controls. From these results, it is concluded that the DXR can be inhibited by the expression of FasL and/or Bcl-2. However, it is necessary to establish more reliable and safe methods to introduce these molecules into in vivo organs before clinical trials.
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