| Co-Investigator(Kenkyū-buntansha) |
BODE Wolfram Max-Planck-Inst.fur Biochemie, Professor
FRITZ Hans Munich Univ., Dept.of Clinical Chem.and Clinical Biochem., Surgical clinic, Professor
TASHIRO Masato Dept.of Virology 1, National Institute of Health, ウイルス第一部, 部長 (90111343)
TOWATARI Takae Div.of Enzyme Chemistry, Inst.for Enzyme Res., The University of Tokushima, 酵素科学研究センター, 助教授 (60108876)
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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 by tryptase Clara of influenza A virus in vitro and in vivo. One is pulmonary surfactant which specifically adsorbed tryptase Clara, resulting in its inactivation but not other trypsin-type proteases, such as trypsin, factor Xa, plasmin and mast cell tryptase. The other compound in the lavage was a 12kDa protein which was identified to be an antileukoprotease (ALP) by the amino acid sequence analysis. ALP inhibited the activity of tryptase Clara, with a Ki value of 9.7 x 10^<-8> M and multi-cycles of mouse-adopted influenza A virus replication in rat lungs in vivo. MPI consists of two homologous domins 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 compounds may be useful for the prevention and treatment of infection with influenza virus.
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