| Project/Area Number |
08557064
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Hematology
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| Research Institution | Mie University |
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Principal Investigator |
SUZUKI Koji Mie University, Faculty of Medicine, Professor, 医学部, 教授 (70077808)
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| Co-Investigator(Kenkyū-buntansha) |
TANABE Masataka Nihon Pharmaceutical Co.,R & D Division, Reserch head, 研究開発本部・東京研究部, 主幹研究員
HAYASHI Tatsuya Mie University, Faculty of Medicine, Assistant Professor, 医学部, 助手 (00242959)
IDO Masaru Mie University, Faculty of Medicine, Lecturer, 医学部, 講師 (90167263)
HONJO Eijiro Nihon Pharmaceutical Co.,R & D Division, Resercher, 研究開発本部・東京研究部, 研究員
武谷 浩之 三重大学, 医学部, 助手 (60222105)
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| Project Period (FY) |
1996 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥14,200,000 (Direct Cost: ¥14,200,000)
Fiscal Year 1998: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1997: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1996: ¥8,000,000 (Direct Cost: ¥8,000,000)
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| Keywords | Protein S / Protein S receptor / Protein S deficiency / C4b-binding protein / Activated protein C / Anticoagulants / Anti-inflammation / Sinusoid endothelial cells / 抗血栓薬 / 抗炎症薬 / 肝障害動物実験モデル / 肝類洞内皮 / ELISA / 活性評価法の開発 / C4b結合蛋白質(C4BP) / モノクローナル抗体 / 血栓症 |
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| Research Abstract |
Protein S, a vitamin K-dependent plasma glycoprotein, plays as anticoagulants by enhancing the activated protein C-catalyzed inactivation of coagulation factors Va and VIIIa, and also by inhibiting the prothrombinase complex formation. Protein S also plays as an anti-inflammatory agent in the in vivo study using experimental animal models. In this project, we studied structural and functional features of protein S to develop protein S as a drug in-aid for anticoagulation and anti-inflammation: (1) We found that rat protein S mRNA expresses strongly in the liver and weakly in the lung, spleen testis and uterus, and that rat plasma protein S and C4b-binding protein (C4BP) behave similarly to human counterparts. The levels of protein S and C4BP in the isolated liver cells were specifically increased by treating with IL-6, and decreased by treating with lipopolysaccharide. These change of protein S was also observed in the isolated sinusoid endothelial cells. Thus the expression of protein S from the sinusoid cells may reflect the level of plasma protein S. (2) We found that protein S receptor exits specifically on the human endothelial cells, and that the receptor is different from annexin II that have been recently reported as a candidate for protein S receptor on vascilar smooth muscle cells.
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