1997 Fiscal Year Annual Research Report

感染におけるマトリックスメタロプロテアーゼの活性化と病態増悪機構

Research Project

Project/Area Number	09470077
Research Institution	Kumamoto University
Principal Investigator	前田浩熊本大学, 医学部, 教授 (90004613)
Co-Investigator(Kenkyū-buntansha)	宮本洋一熊本大学, 医学部, 助手 (20295132) 澤智裕熊本大学, 医学部, 助手 (30284756) 赤池孝章熊本大学, 医学部, 助教授 (20231798)
Keywords	細菌性プロテアーゼ / 病原因子 / matrix metalloproteinase / ブラジキニン / 敗血症
Research Abstract	細菌性プロテアーゼの病原性発現メカニズムの解析を行った。本年度は、特に各種細菌性プロテアーゼによるヒトmatrix metalloproteinase(MMP)の活性化のメカニズムの解明を中心に解析を進めた。あわせて、マウスのVibrio vulnificus敗血症モデルを用いて、ブラジキニンアンタゴニストの治療実験を行った。その結果、各種細菌性プロテアーゼのうち、サーモライシンファミリーに属するコレラ菌プロテアーゼ、緑膿菌エラスターゼがMMPの強い活性化能を有することがわかった。また、これらプロテアーゼは、これまで報告のなかったMMPのアミノ酸残基を認識して、限定分解により特異的にMMPの活性化をもたらしていることがわかった。従って、病原性細菌の産生するいくつかの細胞外プロテアーゼは、宿主のMMPの活性化を介して細菌の生体内侵入を容易にし、その病原性に寄与する可能性が示された。一方、V. vulnificus敗血症モデルにおいて、ブラジキニンアンタゴニストが本菌の血行性播種を抑制し、著明な生存率の改善をもたらした。以上の知見は、細菌性プロテアーゼが宿主の内因性プロテアーゼを活性化し、組織破壊や病原細菌の生体内侵入を容易にしていることを示唆している。

Research Products

(13 results)

All Other

All Publications (13 results)

[Publications] T. Okamoto, et al.: "Activation of human matrix metalloproteinases by various bacterial proteinases" J. Biol. Chem.272. 6059-6066 (1997)
[Publications] H. Muranaka, et al.: "Superoxide scavenging activity of erythromycin-iron complex" Biochem. Biophys. Res. Commun.232. 183-187 (1997)
[Publications] D.C. Hooper, et al.: "Prevention of experimental allergic encephalitis by targeting nitric oxide and peroxynitrite : implications for the treament of multiple sclerosis" Proc. Natl. Acad. Scie. U.S.A. 94. 2528-2533 (1997)
[Publications] K. Umezawa, et al.: "Induction of nitric oxide synthesis and xanthine oxidase and their role in the antimicrobial mechanism against Salmonella typhimurium in mice" Infect. Immun.65. 2932-2940 (1997)
[Publications] K. Maruo, et al.: "Generation of anaphylatoxins through proteolytic processing of C3 and C5 by house dust mite protease" J. Allergy and Clin. Immunol.100. 253-260 (1997)
[Publications] T. Okamoto, et al.: "Activation of human neutrophil procollagenase by nitrogen dioxides and peroxynitrite : A novel mechanism for procollagenase activation involving nitric oxide" Arch. Biochem. Biophys.342. 253-260 (1997)
[Publications] T. Akaike, et al.: "Free radicals in viral pathogenesis : Molecular mechanisms involving superoxide and NO" Proc. Soc. Exp. Biol. Med.217. 64-73 (1998)
[Publications] H. Maeda, et al.: "Human matrix metalloprotease activation by insults of bacterial infection involving proteases and free radicals" Biol. Chem.379. 193-200 (1998)
[Publications] J. Wu, et al.: "Modulation of enhanced vascular permeability in tumors by a bradykinin antagonist, a cyclooxygenase inhibitor, and a nitric oxide scavenger" Cancer Res.58. 159-165 (1998)
[Publications] K. Maruo, et al.: "Involvement of bradykinin generation in intravascular dissemination of Vibrio vulnificus and prevention of invasion by a bradykinin antagonist" Infect. Immun.66. 866-869 (1998)
[Publications] H. Maeda and T. Akaike: "Protease Inhibitors : Novel Therapeutic Application and Development (e d. N. Marcready)" International Business Communications, Inc., Southborough, 33 (1997)
[Publications] H. Maeda, et al.: "Medical Aspects of Proteases and Protease Inhibitors (eds. N. Katunuma, H. Kido, H. Fritz and J. Travis)" IOS Press, Amsterdam, 11 (1997)
[Publications] H. Maeda and T. Akaike: "Nitric Oxide in Transplant Rejection and Anti-tumor Defense (eds. J.L. Zweier and S.J. Lukiewicz)" Kluwer Academic Publishers, Norwell(in press), (1998)

1997 Fiscal Year Annual Research Report

感染におけるマトリックスメタロプロテアーゼの活性化と病態増悪機構

Principal Investigator

前田 浩 熊本大学, 医学部, 教授 (90004613)

Research Products

[Publications] T. Okamoto, et al.: "Activation of human matrix metalloproteinases by various bacterial proteinases" J. Biol. Chem.272. 6059-6066 (1997)

[Publications] H. Muranaka, et al.: "Superoxide scavenging activity of erythromycin-iron complex" Biochem. Biophys. Res. Commun.232. 183-187 (1997)

[Publications] D.C. Hooper, et al.: "Prevention of experimental allergic encephalitis by targeting nitric oxide and peroxynitrite : implications for the treament of multiple sclerosis" Proc. Natl. Acad. Scie. U.S.A. 94. 2528-2533 (1997)

[Publications] K. Umezawa, et al.: "Induction of nitric oxide synthesis and xanthine oxidase and their role in the antimicrobial mechanism against Salmonella typhimurium in mice" Infect. Immun.65. 2932-2940 (1997)

[Publications] K. Maruo, et al.: "Generation of anaphylatoxins through proteolytic processing of C3 and C5 by house dust mite protease" J. Allergy and Clin. Immunol.100. 253-260 (1997)

[Publications] T. Okamoto, et al.: "Activation of human neutrophil procollagenase by nitrogen dioxides and peroxynitrite : A novel mechanism for procollagenase activation involving nitric oxide" Arch. Biochem. Biophys.342. 253-260 (1997)

[Publications] T. Akaike, et al.: "Free radicals in viral pathogenesis : Molecular mechanisms involving superoxide and NO" Proc. Soc. Exp. Biol. Med.217. 64-73 (1998)

[Publications] H. Maeda, et al.: "Human matrix metalloprotease activation by insults of bacterial infection involving proteases and free radicals" Biol. Chem.379. 193-200 (1998)

[Publications] J. Wu, et al.: "Modulation of enhanced vascular permeability in tumors by a bradykinin antagonist, a cyclooxygenase inhibitor, and a nitric oxide scavenger" Cancer Res.58. 159-165 (1998)

[Publications] K. Maruo, et al.: "Involvement of bradykinin generation in intravascular dissemination of Vibrio vulnificus and prevention of invasion by a bradykinin antagonist" Infect. Immun.66. 866-869 (1998)

[Publications] H. Maeda and T. Akaike: "Protease Inhibitors : Novel Therapeutic Application and Development (e d. N. Marcready)" International Business Communications, Inc., Southborough, 33 (1997)

[Publications] H. Maeda, et al.: "Medical Aspects of Proteases and Protease Inhibitors (eds. N. Katunuma, H. Kido, H. Fritz and J. Travis)" IOS Press, Amsterdam, 11 (1997)

[Publications] H. Maeda and T. Akaike: "Nitric Oxide in Transplant Rejection and Anti-tumor Defense (eds. J.L. Zweier and S.J. Lukiewicz)" Kluwer Academic Publishers, Norwell(in press), (1998)

前田浩熊本大学, 医学部, 教授 (90004613)