| Project/Area Number |
10671258
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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 |
Thoracic surgery
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| Research Institution | Osaka University |
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Principal Investigator |
MIYAGAWA Shuji Osaka University Medical School, Associate Professor, 医学系研究科, 助教授 (90273648)
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| Co-Investigator(Kenkyū-buntansha) |
OKABE Masaru Osaka University, Professor, 教授 (30089875)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1999: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1998: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | cell-mediated lysis / swine endothelial cell / HLA-G / NK cell / β2-macroglobulin / β2ミクログロプリン |
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| Research Abstract |
We have investigated the effect of HLA-G and HLA-E to NK-mediated direct cytotoxicity, using hamster ovarian tumor cells (CHO) or swine endothelial cell (SEC) transfectants with these molecules.
At first, cDNA of human full-length HLA-G (G1 and G3), HLA-E and β2-macroglobulin were prepared and subcloned into the pCAGGS (β-actin promoter).
The surface expression of HLA-G (G1) and β2-macroglobulin were confirmed. In addition, co-transfection of β2-microglobulin with HLA-G1 enhanced the level of expression by several times. On the other hand, HLA-G3 was not expressed on the SEC surface.
Concerning HLA-E, the expression was checked by FACS and northern blot. The signal peptide of HLA-E was substituted with that of HLA-G for certain expression.
Amelioration of NK cell-mediated lysis by the transfectant molecules on CHO or SEC was then tested as an in vitro delayed-type rejection model of a discordant xenograft. HLA-G1 and HLA-E significantly suppressed the NK cell mediated SEC lysis.
The expression of HLA-G and/or HLA-E on the cell surface serves as a new approach in overcoming NK-mediated immunity to xenografts.
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