| Project/Area Number |
12470273
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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 |
Thoracic surgery
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| Research Institution | Osaka University |
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Principal Investigator |
SHIRAKURA Ryota Osaka university graduate School of Medicine Professor, 医学系研究科, 教授 (00116047)
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| Co-Investigator(Kenkyū-buntansha) |
MURAKAMI Hiroshi The Animal Engineering Research Institute Research maneger, 研究員
OKABE Masaru Genome Information research center Osaka University Professor, 遺伝情報実験施設, 教授 (30089875)
MIYAGAWA Shuji Osaka university graduate School of Medicine Associate Professor, 医学系研究科, 助教授 (90273648)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥16,100,000 (Direct Cost: ¥16,100,000)
Fiscal Year 2002: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2001: ¥4,100,000 (Direct Cost: ¥4,100,000)
Fiscal Year 2000: ¥7,900,000 (Direct Cost: ¥7,900,000)
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| Keywords | NK cell / HLA-E / HLA-G1 / pig eridothelial cell / hlycosyltransferase / 糖転位酵素 / β_2microglobulin / β2 microglobulin |
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| Research Abstract |
Natural killer (NK) cell mediated response plays an important role in xenograft rejection. The strategy for inhibiting NK cell activity to PEC was investigated using HLA-G and HLA-E on pig endothelial cell (PEC).
1. The transfected HLA-G1 was easily expressed on PEC. The expressed HLA-G1 significantly suppressed NK-mediated PEC cell lysis.
The HLA-G3 was not expressed on PEC. Therefore, the gene introduction of HLA-G3 in PEC showed no protective effect from human NK cells.
2. The PEC transfectant with HLA-E genes did not expressed the HLA molecule. However, the modification of the leader sequence of the HLA-E gene successfully induced the expression of the HLA-E molecule. Furthermore, the transfectant expressed both HLA-G1 and HLA-E molecules, thus efficiently enhancing the inhibition of NK-mediated PEC lysis.
3. The co-effect of HLA-G1 expression and the remodeling of glycoantigens such as the α-Gal epitope by the introduction of glycosyltransferase genes, was evaluated.
The effect of HLA-G1 on NK cell-mediated PEC lysis was lower than that by the glycosyltransferases. In the case of the co-transfectants, such as HLA-G1 + N-acetylglucosaminyltransferase-III and HLA-G1 + α1,2fucosyltransferase, showed significant reductions in direct NK cell-mediated cytotoxicity, compared with the single HLA-G1 transfectant.
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