| Project/Area Number | 05557014 |
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Institute for Enzyme Research, The University of Tokushima |
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Principal Investigator |
KIDO Hiroshi Dept.of Enzyme Chemistry, Institute for Enzyme Research, The University of Tokushima, Professor, 酵素科学研究センター, 教授 (50144978)
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| Co-Investigator(Kenkyū-buntansha) |
NINOMIYA Kenji Product Development Laboratories, Tokyo Tanabe Co., Ltd., Research Head, 研究開発本部, 主任研究員
KAMOSHITA Keiichi Research Laboratories Pharmaceuticals Group, Nippon Kayaku Co., Researcher, 総合研究所, 研究員
SUKENAGA Yoshikazu Research Laboratories Pharmaceuticals Group, Nippon Kayaku Co., Research Head, 総合研究所, 主任研究員
TOWATARI Takae Dept.of Enzyme Chemistry, Institute for Enzyme Research, The University of Tokus, 酵素科学研究センター, 助教授 (60108876)
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| Project Period (FY) |
1993 – 1995
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| Project Status |
Completed(Fiscal Year 1995)
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| Budget Amount *help |
¥18,900,000 (Direct Cost : ¥18,900,000)
Fiscal Year 1995 : ¥4,500,000 (Direct Cost : ¥4,500,000)
Fiscal Year 1994 : ¥5,400,000 (Direct Cost : ¥5,400,000)
Fiscal Year 1993 : ¥9,000,000 (Direct Cost : ¥9,000,000)
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| Keywords | influenza virus / Tryptase Clara / pulmonary surfactant / anti-leucoprotease inhibitor / protease / protease inhibitor / defensive compounds / bronchial lavage / 肺サーファクタント / ヘムアクルチニン / 膜融合 |
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| Research Abstract |
Tryptase Clara, a trypsin-like protease localized exclusively in and secreted from Clara cells of the bronchial epithelium proteolytically activates the infectivity of influenza A virus [H.Kido, Y.Yokogoshi, K.Sakai, M.Tashiro, Y.Kishino, A.Fukutomi and N.Katunuma (1992), J.Biol.Chem.267 : 13573-13579]. In this research project, we found two compounds in human bronchial ravage, which inhibited the proteolytic activation of influenza A virus by tryptase Clara in vitro and in vivo. One is pulmonary surfactant which specifically inhibited tryptase Clara with a Ki value of 1.3 * 10^<-7> M but not other trypsin-type proteases, such as trypsin, factor Xa, plasmin and mast cell trytase. The other compound in the lavage was a 12kDa protein which was identified to be a human mucus protease inhibitor (MPI) by the amino acid sequence analysis. MPI inhibited the activity of tryptase Clara, with a Ki value of 9.7 * 10^<-8> M and multicycles of mouse-adopted influenza A virus replication in rat lungs in vivo. MPI consists of two homologous domains and the C-terminal domain inhibited the virus activation but the N-terminal domain had little effect. Taken together, we found two endogenous local defensive compounds which inhibit proteolytic activation of influenza A virus by tryptase Clara. These compouds may be useful for the prevention and treatment of infection with influenza virus.
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