| Project/Area Number |
12670197
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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 |
Experimental pathology
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| Research Institution | SHINSHU UNIVERSITY |
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Principal Investigator |
NAKAYAMA Jun SHINSHU UNIVERSITY, Graduate School of Medicine, Associate Professor, 大学院・医学研究科, 助教授 (10221459)
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| Co-Investigator(Kenkyū-buntansha) |
KAWASAKI Seiji SHINSHU UNIVERSITY, School of Medicine, Professor, 医学部, 教授 (80177667)
KATSUYAMA Tsutomu SHINSHU UNIVERSITY, School of Medicine, Professor, 医学部, 教授 (90020809)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2001: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2000: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | liver transplantation / acute rejection / lymphocyte homing / L-selectin / O-glycan / glycosyltransferase / ο-グリカン / 拒絶反応 / セレクチン |
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| Research Abstract |
We have tested if lymphocyte homing mechanism mediated by L-selectin is involved in the pathogenesis of acute rejection of transplanted liver. Liver samples biopsied just after the transplantation as well as showing the acute rejection were immunostained with MECA-79 antibody specific for peripheral node addressin ( PNAd ). In 2 of 8 patients, PNAd was found to be expressed only in the endothelial cells in portal area exhibiting acute rejection. Since L-selectin ligand, 6-sulfo sialyl Lewis X is present in the terminal end of core2 O-glycans, the presence of core2β6GlcNAcT-l ( C2GnT-l ), a key enzyme for the biosynthesis of core2 O-glycans was analyzed by immunohistochemistry using antisera against C2GnT-l. As results, C2GnT was not detectable in the endothelial cells positive for PNAd. In addition, these endothelial cells were not recognized by HECA-452 antibody specific for Lewis X-related carbohydrates including 6-sulfo sialyl Lewis X. In a collaborative study with Professor Minoru Fukuda at the Burnham Institute, it is shown that PNAd is Galβ1→4( sulfo→6 )GlcNAcβ1→3Galβ1→3GalNAc by cloning a novel glycosyltransferase, corel extension β1, 3GlcNAcT. The same study also demonstrates that 6-sulfo sialyl Lewis X is expressed in the terminal ends of not only core2 O-glycans but also extended corel O-glycans and serves as ligand for L-selectin. Taken together, the present study indicates that PNAd can be expressed in the endothelial cells showing acute rejection. However, 6-sulfo sialyl Lewis X was not expressed in the PNAd-positive endothelial cells, suggesting that the L-selectin-mediated lymphocyte homing is barely involved in the pathogenesis of acute rejection of the transplanted liver.
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