1992 Fiscal Year Annual Research Report

細菌毒素の宿主細胞に対する作用の分子機構

Research Project

Project/Area Number	04304032
Research Institution	Jichi Medical University
Principal Investigator	中野昌康自治医科大学, 医学部, 教授 (70048958)
Co-Investigator(Kenkyū-buntansha)	野田公俊千葉大学, 医学部, 教授 (60164703) 中村信一金沢大学, 医学部, 教授 (90019620) 光山正雄新潟大学, 医学部, 教授 (10117260) 木下タロウ大阪大学, 微生物病研究所, 教授 (10153165) 竹田美文京都大学, 医学部, 教授 (30029772)
Keywords	細菌毒素 / 内毒素 / 外毒素 / 細胞傷害 / LPS / 蛋白毒素 / GPIアンカー
Research Abstract	1.細胞内毒素(LPS,microcystin):LPSのreceptor構成蛋白の一つCD14の膜結合構造GPI anchorの生合成の初期に働く遺伝子PIG-AのcDNA cloning に成功し(木下)、LPSによるマクロフアージ活性化に際してリン酸化される細胞質内pp65蛋白がprotein kinase Cあるいはcalmodulin-dependent kinaseを介してのmonokine(IL-1,TNF)産生とかかわっており(中野)、微量LPS前処理マクロフアージの、その後、LPS前処理マクロフアージの、その後のLPS刺激によるTNF-α産生の抑制は、TNF-α遺伝子発現に必要なDNA結合蛋白NF-kappaBの活性化の抑制に基づくことを明かにした(赤川)。非発熱性lipid A類緑体の前処置でも、その後のLPS刺激によるTNF-αやIL-1βのmRNAの発現は抑制され、pp65のリン酸化も阻害される(中野)。mannose homo O多糖体部分をもつLPSは、自己免疫病変を誘導でき(横地)、P. gingivalisのLPSはLPS非応答性C3H/HeJマウスのリンパ球やマクロファージを活性化できること(浜田)、microcystinは微量ながら菌体外へ分泌されることを見いだした(白井)。 2.外毒素:Vero毒素の遺伝子の塩基を置換し、無毒変異毒素を作製(竹田)、C. dfficileの菌体内toxin Aの精製(中村)、A群レンサ球菌発熱性毒素A,B,C,Dの同時精製法の開発(五十嵐)、耐熱性下痢原因毒素ST2の活性測定法の確立(岡本)、耐熱性腸菅毒素STのcloning(平山)、ジフテリア毒素受容体関連蛋白DRAP27のcloning(目加田)に成功した。腸炎ビブリオ耐熱溶血毒は2段階穴形成毒素であり(本田)、コレラ毒素は標的細胞内で2種類の蛋白で毒性が制御され(野田)、緑膿菌プロテアーゼはそのキニン生成能による菌血症促進作用を発現し(前田)、破傷風毒素の作用にcalmodulinが関与し(松田)、リステリア溶血毒は細胞膜障害作用とIL-I誘導作用が見られ(光山)、エルシニア毒素はスーパー抗原活性を有すること(内山)を明かにした。

Research Products

(19 results)

All Other

All Publications (19 results)

[Publications] Miyata,T. et al.: "The cloning of PIG-A, a component in the early step of GPI-anchor biosynthesis" Science. (1993)
[Publications] Nakano, M. et al.: "Intracellular protein phosphorylation in murine peritoneal macropgages in response to bacterial lipopolysaccharide (LPS)" Immunobiology. (1993)
[Publications] Nagao, S. et al.: "Species dependency of in vitro macrophage activation by bacterial peptidoglycans" Microbiol. Immunol.36. 1155-1171 (1992)
[Publications] Yokochi, T. et al.: "Novel adjuvant action of lipopolysaccharides that possess mannose homopolysaccharides as O-specific polysaccharides on immune response to nonimmunogenic antoantigens in mice" Infect. Immun.60. 4953-4956 (1992)
[Publications] Ogawa, T. et al.: "Immunochemical and biological characterization of outer membrane proteins of Porphyromonas endodontalis" Inect. Immun.60. 4528-4533 (1992)
[Publications] Karasawa, T. et al.: "Distribution of zot(zonula occludens toxin)gene in strains of Vibrio cholerae 01 and non-01." FEMS Microbiology Letters. (1993)
[Publications] Meng, X. Q. et al.: "Purification and characterization of intracellular toxin A of Clostridium difficile" J. Med. Microbiol.38. 69-73 (1993)
[Publications] Hitotsubashi, S. et al.: "Some properties of purified Escherichia coli heat-stable enterotoxin II" Infect. Immun.60. 4468-4474 (1992)
[Publications] Hirayama, t. et al.: "Glycoprotein recep for a heat-stable enterotoxin(STh) produced by enterotoxigenic Escherichia coli" Infect. Immun.60. 4213-4220 (1992)
[Publications] Mitamura, T. et al.: "THe 27-kD diphtheria toxin receptor-associated protein(DRAP27) from vero cells is the monkey homologoue of human CD9 antigen" J. Cell Biol.118. 1389-1399 (1992)
[Publications] Honda, T. et al.: "The thermostable direct hemolysin of Vibrio parahemolytics is a pore-forming toxin" Can. J. Microbiol.38. 1175-1180 (1992)
[Publications] 野田公俊: "コレラ毒素のADP-リボシル化活性を制御する諸因子" 日本細菌学雑誌. 47. 367-372 (1992)
[Publications] Maeda, H. et al.: "Microbial proteinases as a universal trigger of kinin generation" Recent Progress on kinins, agents and actions. Supplements. 38/III-II. 362-369 (1992)
[Publications] Tsukada, H. et al.: "Induction of macrophage interleukin-1 production by Listeria monocytogenes hemolysin" Cellular Immunol.140. 21-30 (1992)
[Publications] Imanishi, K. et al.: "Relative ability of destinct isotypes of human major histocompatibility complex class II molecules to bind streptococcal pyrogenic exotoxin types A and B" Infect. Immun.60. 5025-5029 (1992)
[Publications] Nakano, M.,and Shinomiya, H.(分担)(Morrison, D. C.,and Ryan, J. L.編集): "Bacterial Endotoxic Lipopolysaccharides,Vol.1.Molecular Biochemistry and Cellular Biology" CRC Press, 449 (1992)
[Publications] 徳永徹、吉田彪、赤川清子(編): "マクロフアージ実験マニュアル" 講談社サイエンティフィック, 250 (1992)
[Publications] Noda,M.,and Kato, I.(分担)(Niwa, M.編集): "Oji International Seminar on ADP-Ribosylation Reaction-Mechanism and Biological Function" Oji International Seminar, 66 (1992)
[Publications] Matsuda,M. et al.(分担)(DasGupta, B. R.編集): "Botulisnum and Tetanus Neurotoxins" Plenum Publishing Co., (1992)

1992 Fiscal Year Annual Research Report

細菌毒素の宿主細胞に対する作用の分子機構

Principal Investigator

中野 昌康 自治医科大学, 医学部, 教授 (70048958)

Research Products

[Publications] Miyata,T. et al.: "The cloning of PIG-A, a component in the early step of GPI-anchor biosynthesis" Science. (1993)

[Publications] Nakano, M. et al.: "Intracellular protein phosphorylation in murine peritoneal macropgages in response to bacterial lipopolysaccharide (LPS)" Immunobiology. (1993)

[Publications] Nagao, S. et al.: "Species dependency of in vitro macrophage activation by bacterial peptidoglycans" Microbiol. Immunol.36. 1155-1171 (1992)

[Publications] Yokochi, T. et al.: "Novel adjuvant action of lipopolysaccharides that possess mannose homopolysaccharides as O-specific polysaccharides on immune response to nonimmunogenic antoantigens in mice" Infect. Immun.60. 4953-4956 (1992)

[Publications] Ogawa, T. et al.: "Immunochemical and biological characterization of outer membrane proteins of Porphyromonas endodontalis" Inect. Immun.60. 4528-4533 (1992)

[Publications] Karasawa, T. et al.: "Distribution of zot(zonula occludens toxin)gene in strains of Vibrio cholerae 01 and non-01." FEMS Microbiology Letters. (1993)

[Publications] Meng, X. Q. et al.: "Purification and characterization of intracellular toxin A of Clostridium difficile" J. Med. Microbiol.38. 69-73 (1993)

[Publications] Hitotsubashi, S. et al.: "Some properties of purified Escherichia coli heat-stable enterotoxin II" Infect. Immun.60. 4468-4474 (1992)

[Publications] Hirayama, t. et al.: "Glycoprotein recep for a heat-stable enterotoxin(STh) produced by enterotoxigenic Escherichia coli" Infect. Immun.60. 4213-4220 (1992)

[Publications] Mitamura, T. et al.: "THe 27-kD diphtheria toxin receptor-associated protein(DRAP27) from vero cells is the monkey homologoue of human CD9 antigen" J. Cell Biol.118. 1389-1399 (1992)

[Publications] Honda, T. et al.: "The thermostable direct hemolysin of Vibrio parahemolytics is a pore-forming toxin" Can. J. Microbiol.38. 1175-1180 (1992)

[Publications] 野田 公俊: "コレラ毒素のADP-リボシル化活性を制御する諸因子" 日本細菌学雑誌. 47. 367-372 (1992)

[Publications] Maeda, H. et al.: "Microbial proteinases as a universal trigger of kinin generation" Recent Progress on kinins, agents and actions. Supplements. 38/III-II. 362-369 (1992)

[Publications] Tsukada, H. et al.: "Induction of macrophage interleukin-1 production by Listeria monocytogenes hemolysin" Cellular Immunol.140. 21-30 (1992)

[Publications] Imanishi, K. et al.: "Relative ability of destinct isotypes of human major histocompatibility complex class II molecules to bind streptococcal pyrogenic exotoxin types A and B" Infect. Immun.60. 5025-5029 (1992)

[Publications] Nakano, M.,and Shinomiya, H.(分担)(Morrison, D. C.,and Ryan, J. L.編集): "Bacterial Endotoxic Lipopolysaccharides,Vol.1.Molecular Biochemistry and Cellular Biology" CRC Press, 449 (1992)

[Publications] 徳永 徹、吉田 彪、赤川 清子(編): "マクロフアージ実験マニュアル" 講談社サイエンティフィック, 250 (1992)

[Publications] Noda,M.,and Kato, I.(分担)(Niwa, M.編集): "Oji International Seminar on ADP-Ribosylation Reaction-Mechanism and Biological Function" Oji International Seminar, 66 (1992)

[Publications] Matsuda,M. et al.(分担)(DasGupta, B. R.編集): "Botulisnum and Tetanus Neurotoxins" Plenum Publishing Co., (1992)

中野昌康自治医科大学, 医学部, 教授 (70048958)

[Publications] 野田公俊: "コレラ毒素のADP-リボシル化活性を制御する諸因子" 日本細菌学雑誌. 47. 367-372 (1992)

[Publications] 徳永徹、吉田彪、赤川清子(編): "マクロフアージ実験マニュアル" 講談社サイエンティフィック, 250 (1992)