| Project/Area Number |
07044239
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Institution | KANAZAWA UNIVERSITY |
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Principal Investigator |
NAKANUMA Yasuni KANAZAWA UNIVERSITY SCHOOL OF MEDISINE, 医学部, 教授 (10115256)
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| Co-Investigator(Kenkyū-buntansha) |
SAITO Katsuhiko KANAZAWA UNIVERSITY SCHOOL OF MEDISINE, 医学部, 非常勤講師 (10205635)
SASAKI Motoko KANAZAWA UNIVERSITY SCHOOL OF MEDISINE, 医学部, 助手 (70225895)
TERASAKI Syuuichi KANAZAWA UNIVERSITY SCHOOL OF MEDISINE, 医学部, 助手 (10251943)
TERADA Tadashi KANAZAWA UNIVERSITY SCHOOL OF MEDISINE, 医学部, 助教授 (30188677)
GERSHWIN M E 米国, 加州大学・Davis校, 教授
MERIC Gershwin UNIVERSITY OF CALIFORNIA DAVIS
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| Project Period (FY) |
1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1995: ¥3,800,000 (Direct Cost: ¥3,800,000)
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| Keywords | primary biliary cirrhosis / antimitochodrial antibodies / interlobular bile duct / confocal lazer microscope / pyruvate dehydrogenase / bile / ALY mouse / immunohistochemistry / Immunopathological |
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| Research Abstract |
It has been recently reported that pyruvate dehydrogenase E2 subunit (PDC-E2), a major autoantigen recognized by antimitochodrial antibodies frequently and characteristically occurring in the patients with primary biliary cirrhosis (PBC), was abnormally expressed on the interlobular bile duct in PBC.T cells reating with this antigen were also recovered from PBC liver tissues. In this international collaborative project, these phenomena were examined using a monoclonal antibody reacting with inner lipoic domain of PDC-E2 and immunohistochemistry including confocal lazer microscope, in situ hybridization, and western blotting of bile. It was found out that this antigen was abnormally expressed on the luminal side of damaged interlobular bile ducts, outside mitochondria, while expression of this antigen on the bile ducts in other diseases was focal or weak. mRNA for this antigen was hardly detectable in the bile duct epithelial cells of PBC which were expressing this antigen, though mRNA was detectable in hepatocytes and other mesenchymal cells. Substance (s) cross-reacting with PDC-E2, about 74kD molecular weight, were detectable frequently in bile from PBC patients. In addition, a novel model of PBC is being explored. In this animal (ALY mouse), there were a spontaneous occurrence of nonsuppurative cholangitis and also immunological abnormalities. These results suggest that substances reactive with C355.1 abnormally appeared in bile and abosrbed into the interlobular bile ducts in PBC.It remains unlcear where these substances are produced and how these substances are abnormally absorbed into the bile duct epithelial cells in PBC.The fine mechanism between abnormal expression of PDC-E2 on the bile ducts and host immune system deserve further study.
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