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Molecular biology on murine macrophage activated by bacterial infection or bacterial components

Research Project

Project/Area Number 03454184
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field 細菌学
Research InstitutionJichi Medical School

Principal Investigator

NAKANO Masayasu  JICHI MEDICAL SCHOOL, DEPARTMENT OF MICROBIOLOGY, PROFESSOR, 医学部, 教授 (70048958)

Co-Investigator(Kenkyū-buntansha) SAITO Shinji  JICHI MEDICAL SCHOOL, DEPARTMENT OF MICROBIOLOGY, ASSISTANT, 医学部, 助手 (50195989)
MATSUURA Motohiro  JICHI MEDICAL SCHOOL, DEPARTMENT OF MICROBIOLOGY, ASSOCIATE PROFESSOR, 医学部, 助教授 (20150089)
Project Period (FY) 1991 – 1992
Project Status Completed (Fiscal Year 1992)
Budget Amount *help
¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 1992: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1991: ¥4,800,000 (Direct Cost: ¥4,800,000)
KeywordsBacterial Infection / Bacterial Lipopolysaccharide (LPS) / Macrophages / Protein Phosphorylation / Plastin / Legionella / Salmonella / Monokine / 腫瘍壊死因子(TNF) / 緑膿菌 / マクロファ-ジ / Lーアルギニン
Research Abstract

(1) The most dominantly phosphorylated cytosolic protein, 65kDa protein (pp65), in the murine (C3H/HeN) peritoneal macrophages after stimulation with bacterial lipopolysaccharide (LPS) was isolated and purified. It was a substrate of serine kinase and possessed the amino acid sequences similar to human L-plastin. This protein was also found in the bone marrow cells, liver cells (presumably Kupffer cells) and spleen cells, while it could not be seen in the red blood cells and thymocytes. Identical protein was detected in the peritoneal macrophages of LPS-low responder C3H/HeJ mice. However, the protein in C3H/HeJ macrophages was unable to be phosphorylated by the stimulation with LPS. The posphorylation of pp65 was affected by inhibitors (IH) of protein kinase C (PKC) or calmodulin-dependent kinase, though it was not affected by IH of tyrosine kinase. PKC IH affected the expression of TNF-alpha and IL-1beta mRNA and the production their active molecules. However, calmodulin-dependent IH inhibited mRNA expression and production of IL-1, but did not inhibit those of TNF. Furthermore, the previous treatment of macrophages with nonpyrogenic lipid A analogues induced refractory states on pp65 phosporylation to LPS stimulation.
(2) Murine peritoneal macrophages that had been infected with virulent strain of Legionella pneumophila or Salmonella typhimurium exhibited the protein phosphorylation of pp76(L. p.) or pp85 and 72 (S. t.) which was specific to the infection of these organisms. Live organisms themselves or Heat-killed organisms of these strains did not cause the phosphorylation.
(3) It was demonstrated that cytokines such as TNF-alpha, TNF-beta, IL-1beta and IL-6 enhanced the killing of the organisms of Salmonella or Pseudomonas aeruginosa by the peritoneal macrophages of mice.

Report

(3 results)
  • 1992 Annual Research Report   Final Research Report Summary
  • 1991 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] Nakano,M.,et al.: "Intracellular protein phosphorylation in murine peritoneal macrophage in response to vacterial lipopolysaccharida(Lps);Effects of kinase-inhibiters and Lps-induced tolerance." Immunobiology. (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Yamamoto,Y.,et al.: "Infection of macrophages with Legionella pneumophila induces phosphorylation of 76-kiodalton protein." Infect.Immun.60. 3452-3455 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Nakano,M.,et al.: "Protective effects of cytokines in murine salmonellosis." Adv.Exp.Med.Biol.319. 87-95 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 中野 昌康: "エンドトキシンによるマクロファージ活性化の分子機構" 日本Shock学分雑誌. 7. 18-30 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 中野 昌康他(分担): "医学微生物学の新しい展開" (加藤延夫編集)菜根出版, (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Nakano,M.(分担): "Bacterial Endotoxic Lipopolysaccharides,Volum I,Molecular Biochemistry and Cellular Biology" (Eds.by D.C.Morrison and J.L.Ryan)CRC Press,Florida, 449 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Nakano, M., Saito, S., Nakano, Y., Yamasu, H., Matsuura, M., and Shinomiya, H.: "Intracellular protein phosphorylation in murine peritoneal macrophages in response to bacterial lipopolysaccharide (LPS): Effects of kinase-inhibitors and LPS-induced tolerance." Immunobiology. (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Yamamoto, Y., Klein, T. W., Shinomiya, H., Nakano, M., and Friedman, H.: "Infection of macrophages with Legionella pneumophila induces phosphorylation of 76-kilodalton protein." Infect. Immun.60. 3452-3455 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Nakano, M., Onozuka, K., Yamasu, H., Wang, F. Z., Nakano, Y.: "Protective effects of cytokines in murine salmonellosis. Adv." Exp. Med. Biol.319. 87-95 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Nakano, M., and Shinomiya, H.: "The Lps mutational defect in C3H/HeJ mice." In Bacterial Endotoxic Lipopolysaccharides. Volume I, Molecular Biochemistry and Cellular Biology (Eds. by D. C. Morrison and J. L. Ryan) (CRC Press, Florida). 311-328 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Shinomiya, H., Hirata, H., and Nakano, M.: "Purification and characterization of the 65-kDa protein phosphorylated in murine macrophages by stimulation with bacterial lipopolysaccharide." J. Immunol.146. 3617-3625 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Nakano, M., Onozuka, K., Sakamoto, K., Nakano, Y., Shinomiya, H., and Saito-Taki, T.: "Protective effect of cytokines in mice to Pseudomonas aeruginosa infection. Antibiot." Chemother.44. 196-202 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Saito, S., Onozuka, K., Shinomiya, H., and Nakano, M.: "Sensitivity of bacteria to NaNO_2 and to L-arginine-dependent system in murine macrophages." Microbiol. Immunol.35. 325-329 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Shinomiya, H., Hirata, H., Shinomiya, M., and Nakano, M: "Role of endotoxin-stimulated macrophages in liver injury: Molecular mechanisms of macrophage-activation by endotoxin." Frontiers of Mucosal Immunology (Eds. by M. Tsuchiya et al.) Elsevier Science Publisher B. V.359-362 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Yamamoto,Y.: "Infection of macrophages with Legionella pneumophila induces phosphory lation of a 76-kilodalton protein" Infect.Immun.60. 3452-3455 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Nakano,M.: "Intracellular protein phosphorylation in murine peritoneal macrophagas in response to bacterial lipopoly saccharide(LPS)." Immunobiology.

    • Related Report
      1992 Annual Research Report
  • [Publications] 中野 昌康: "エンドトキシンによるマクロファージ活性化の分子機構" 日本shock学会雑誌. 7. 18-30 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Nakano.M,(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)

    • Related Report
      1992 Annual Research Report
  • [Publications] 中野 昌康(分担) (加藤 延夫 編集): "医学微生物学の新しい展開1993" 菜根出版,

    • Related Report
      1992 Annual Research Report
  • [Publications] Saito,S.et al.: "Sensitivity of bacteria to NaNO_2 and to Lーarginineーdependent system in murine macrophages" Microbiol.Immunol.35. 325-329 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Shinomiya.H.et al.: "Purification and characterization of the 65ーkDa protein phosphorylated in murine macrophages by stimulation with bacterial lipopolysaccharide." J.Immunol.146. 3617-3625 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Shinomiya,H.et al.: "Role of endotoxinーstimulated macrophages in liver injury;Molecular mechanisms of macrophageーactivation by endotoxin." Frontiers of Mucosal Immunity,Eds.by M.Tsuchiya et al.Elsevier Science Publishers. 2. 359-362 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Nakano,M.et al.: "Protective effect of cytokines in mice to Pseudomonas aeruginosa infection." Antibiot.Chemother.44. 196-202 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Matsuura,M.et al.: "Enhancement of nonspecific resistance against microbial infections with special reference to Pseudomonas aeruginosa infection by chemically synthesized lipid Aーsubunit analogs." Antibiot.Chemother.44. 203-208 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Nakano,M.et al.: "Protective effects of cytokines in murine salmonellosis." Microbial Infections;Role of Biological Response Modifiers,Eds.by H.Friedman and T.klein,Plenum Press. (1992)

    • Related Report
      1991 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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