| Project/Area Number |
06454258
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Gastroenterology
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| Research Institution | Saitama Medical School |
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Principal Investigator |
FUJIWARA Kenji Saitama Medical School, Faculty of Medicine, Professor, 医学部, 教授 (80101088)
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| Co-Investigator(Kenkyū-buntansha) |
MOCHIDA Satoshi Saitama Medical School, Faculty of Medicine, Assistant Professor, 医学部, 講師 (20219968)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥7,300,000 (Direct Cost: ¥7,300,000)
Fiscal Year 1995: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1994: ¥5,500,000 (Direct Cost: ¥5,500,000)
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| Keywords | fulminant hepatitie / acute liver failure / sinusoidal fibrin doposition / Kupffer cells / sinusoidal endothetial cells / 肝移植 / primary graft nonfunction / トロンボモジュリン / 組織因子 / 肝マクロファージ / 肝類洞内皮細胞 |
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| Research Abstract |
Massive hepatic necrosis, characteristic of fulminant viral hepatitis, occurs as a result of microcirculatory disturbance due to deranged blood coagulation equilibrium between Kupffer cells and sinusoidal endothelial cells. Anticoagulant activity in the hepatic sinusoids was decreased compared to the vessels in other organs as a consequence of no or extremely reduced expressionof tissue factor pathway inhibitor (TFPI) and thrombomodulin (TM) on endothelial cells. Thus, the replacement of TFPI and TM might be a powerful therapy for such liver injury. When rats received recombinant human TFPI intravenously, TFPI disappeared from the circulation rapidly after the injection, and were detected on the surface of sinusoidal endothelial cells and microvilli of hepatocytes, suggesting that TFPI may act as an anticoagulant exclusively on the sinusoidal walls. TM was designed to exert its action enhanced on sinusoidal endothelial cells by expression as a targeting gene through mannose receptors. Intraportal injection of miscells containing mannose and FITC on the surface produced fluorescence products on the lining of sinusoidal walls. These anticoagulant devices targeting hepatic sinusoidal walls may be therapeutic candidates for fulminant viral hepatitis with minimal adverse effects of general bleeding.
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