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A STUDY OF TYPE II ALVEOLAR EPITHELIAL CELLS AS INFECTION SITE OF ACID-FAST BACILLI

Research Project

Project/Area Number 10670545
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionSHIMANE MEDICAL UNIVERSITY

Principal Investigator

SATO Katsumasa  SHIMANE MEDICAL UNIVERSITY, MICROBIOLOGY AND IMMUNOLOGY, INSTRUCTOR, 医学部, 助手 (00142331)

Co-Investigator(Kenkyū-buntansha) SHIMIZU Toshiaki  SHIMANE MEDICAL UNIVERSITY, MICROBIOLOGY AND IMMUNOLOGY, INSTRUCTOR, 医学部, 助手 (60284030)
TOMIOKA Haruaki  SHIMANE MEDICAL UNIVERSITY, MICROBIOLOGY AND IMMUNOLOGY, PROFESSOR, 医学部, 教授 (40034045)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2000: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1999: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1998: ¥1,000,000 (Direct Cost: ¥1,000,000)
KeywordsACID-FAST BACIL II / MYCOBACTERIUM TUBERCULOSIS / MYCOBACTERIUM AVIUM COMPLEX / TYPE II ALVEOLAR EPITHELIAL CELLS / MACROPHAGES / A-549 CELLS / INVASION / CYTOKINES / Mycobacterium avium complex / A-549 細胞 / 抗菌剤
Research Abstract

1. Antimicrobial effects of clarithromycin (CAM), KRM-1648 (KRM) and levofloxacin (LVFX) against Mycobacterium tuberculosis (MTB) or M.avium complex (MAC) residing in the A-549 human type II alveolar epithelial cells (A-549 cells) were less than the effects of the same drugs against the same organisms residing in Mono Mac 6 human macrophage-like cells (MM6-MΦ).
2. Antimicrobial activities of these drugs against MTB and MAC adapted to an intramacrophagic environment (intracellularly adapted : I-type) and those passaged in the 7H9 liquid medium (extracellularly adapted : E-type) were studied. The antibacterial effect of CAM or LVFX against E-type MTB or MAC residing in MM6-MΦs or A-549 cells was stronerg than a case against I-type MTB or MAC within the same cells. On the other hand, the antibacterial effect of KRM for E-type MTB or MAC residing in both cells was weaker than a case for I-type organisms within the same cells.
3. Mice were infected intratracheally with MTB or MAC, and the lung sections of the infected mice were observed with transmission electron photomicrographs. The infected bacteria were recognized in type II alveolar epithelial cells in addition to mature granulocytes and macrophages.
4. Using a dual chamber system, we examined whether the humoral factor of the A-549 cells infected with MTB or MAC which were released, influenced the anti-MTB or the anti-MAC antibacterial activity of MM6-MΦs. The number of the MTB or MAC organisms residing in MM6-MΦs of the top-chamber was decreased by the existence of A-549 cells infected with the MTB or MAC.
5. It was found that the humoral factor (s) that decreased the number of these bacteria might be TNF-α and/or GM-CSF with RT-PCR examination.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (31 results)

All Other

All Publications (31 results)

  • [Publications] Katsumasa Sato: "Antimicrobial activities of benzoxazinorifamycin KRM-1648, clarithromycin and levofloxacin against intracellular Mycobacterium avium complex phagocytosed by murine peritoneal macrophages"Journal of Antimicrobial Chemotherapy. 41. 77-83 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 佐藤勝昌: "結核治療における新薬の展望.キノロン,リファマイシン,マクロライド剤のin vitro抗結核菌および抗MAC抗菌活性,特にin vivo治療効果との関連から"結核. 74. 63-70 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Katsumasa Sato: "Antimicrobial activities of benzoxazinorifamycin (KRM-1648) and clarithromycin against Mycobacterium avium-intracellulare complex within murine peritoneal macrophages, human macrophage-like cells and human alveolar epithelial cells"Journal of Antimicrobial Chemotherapy. 43. 351-357 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 佐藤勝昌: "肺胞上皮細胞およびマクロファージ内での結核菌とMycobacterium avium complexの増殖能について"結核. 74. 655-660 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Katsumasa Sato: "Antimicrobial activities of levofloxacin, clarithromycin, and KRM-1648 against Mycobacterium tuberculosis and Mycobacterium avium complex replicating within Mono Mac 6 human macrophage and A-549 type II alveolar cell lines"International Journal of Antimicrobial Agents. 16. 25-29 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 佐藤勝昌: "抗酸菌のマクロファージ(MΦ)と肺胞上皮細胞への感染性と細胞内増殖性:MΦ内順化菌を用いての検討"結核. 76. 53-57 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Katsumasa Sato: "Antimicrobial activities of benzoxazino-rifamycin KRM-1648, clarithromycin and levofloxacin against intracellular Mycobacterium avium complex phagocytosed by murine peritoneal macrophages."Journal of Antimicrobial Chemotherapy. 41. 77-83 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Katsumasa Sato: "Prospects for development of new anti-microbials for clinical control of tuberculosis. In vitro antimicrobial activities of quinolones, refamycins and macrolides against Mycobacterium tuberculosis and M.avium complex : Attempt to establish new assay methods which accurately reflect therapeutic effects of test agents in vivo"Kekkaku. 74. 63-70 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Katsumasa Sato: "Antimicrobial activities of benzoxazinorifamycin (KRM-1648) and clarithromycin against Mycobacterium avium-intracellulare complex within murine peritoneal macrophages, human macro-phage-like cells and human alveolar epithelial cells Chemotherapy"Journal of Antimicrobial. 43. 351-357 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Katsumasa Sato: "Internalization and replication of Mycobacterium tuberculosis and M.avium complex within type II alveolar epithelial cell line"Kekkaku. 74. 655-660 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Katsumasa Sato: "Antimicrobial activities of levofloxacin, clarithromycin, and KRM-1648 against Mycobacterium tuberculosis and Mycobacterium avium complex replicating within Mono Mac 6 human macrophage and A-549 type II alveolar cell lines"International Journal of Antimicrobial Agents. 16. 25-29 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Katsumasa Sato: "Invasion and intracellular growth of Mycobacterium tuberculosis and Mycobacterium avium complex adapted to intramacrophagic environment within macrophages and type II alveolar epithelial cells"Kekkaku. 76. 53-57 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Haruaki Tomioka: "Comparative antimicrobial activities of the newly synthesized quinolone WQ-3034, levofloxacin, sparfloxacin, and ciprofloxacin against Mycobacterium tuberculosis and Mycobacterium avium complex."Antimicrobial Agents and Chemotherapy. 44. 283-286 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Katsumasa Sato: "Antimicrobial activities of levofloxacin, clarithromycin, and KRM-1648 against Mycobacterium tuberculosis and Mycobacterium avium complex within Mono Mac 6 human macrophage and A-549 type II alveolar cell lines."International Journal of Antimicrobial Agents. 16. 25-29 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Chiaki Sano: "Effects of secretory leukocyte protease inhibitor on the production of the anti-inflammatory cytokines, IL-10 and transforming growth factorbeta(TGF-β), by lipopolysaccharide-stimulated macrophage"Clinical and Experimental Immunology. 121. 77-85 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 赤木竜也: "マウス腹腔マクロファージのin vitro培養に伴う抗結核菌活性の変化について"結核. 75. 477-482 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Haruaki Tomioka: "Roles of tumour necrosis factor-alpha(TNF-α), transforming growth factor-beta(TGF-β), and IL-10 in the modulation of intercellular adhesion molecul-1(ICAM-1) expression by macrophages during mycobacterial infection"Clinical and Experimental Immunology. 122. 335-342 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 佐藤勝昌: "抗酸菌のマクロファージ(MΦ)と肺胞上皮細胞への感染性と細胞内増殖性:MΦ内順化菌を用いての検討"結核. 76. 53-57 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Sano Chiaki: "The modulating effects proinflammatory cytokines interferon-gamma(IFN-γ) and tumour necrosis factor-alpha(TNF-α),and immunoregulating cytokines IL-10 and transforming growth factor-beta(TGF-β), on anti-microbial activity of murine peritoneal macrophages against Mycobacterium avium-intracellulare complex"Clinical and Experimental Immunology. 115. 435-442 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 佐野千晶: "Secretory leukocyte protease inhibitorによるマクロファージ機能の修飾:LPS刺激およびMycobacterium avium complex刺激マクロファージのサイトカインおよびnitric oxide産生能に及ぼす作用について"結核. 74. 563-570 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 佐藤勝昌: "マクロファージおよびII型肺胞上皮細胞内の結核菌あるいはMycobacterium avium complexに対する各種薬剤の抗菌効果"結核. 74. 571-577 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 佐藤勝昌: "細胞上皮細胞およびマクロファージ内での結核菌とMycobacterium avium complexの増殖能について"結核. 74. 655-660 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 冨岡治明: "マウス腹腔マクロファージの抗Mycobacterium avium complex殺菌能に及ぼすIL-10およびTGF-βの影響について"乳酸菌研究会に関する報告書(平成10年度). 472-476 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tomioka Haruaki: "Comparative in vitro antimicrobial activities of the newly synthesized quinolone HSR-903,sitafloxacin (Du6859-a),gatifloxacin(AM-1155),and levofloxacin against Mycobacterium tuberculosis and Mycobacterium avium complex."Antimicrobial Agents and Chemotherapy. 43. 3001-3004 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Sato Katumasa: "Differential potentiation of anti-mycobacterial activity and reactive nitrogen intermediate-producing ability of murin peritoneal macrophages activated by interferon-gamma and tumor necrosis facter-alpa." Clinical Experimental Immunology. 112. 63-68 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Emori Masako: "Evaluation of in vivo therapeutic efficacy of a new benzoxazinorifamycin,KRM-1648,in SCID mouse model for disseminated Mycobacterium avium complex infection" International Journal of Antimicrobial Agents. 10. 59-65 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Sato Katumasa: "Antimicrobial activities of benzoxazinorifamycin KRM-1648,clarithromycin and levofloxacin against intracellular Mycobacterium avium complex phagocytosed by murine peritoneal macrophages" Journal of Antimicrobial Chemotherapy. 41. 77-83 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Sano Chiaki: "Therapeutic effects of benzoxazinorifamycin KRM-1648 administered alone or in combination with a half-sized secretory leukocyte protease inhibitor or the nonsteroidal anti-inflammatory drug diclofenac. sodium against Mycobacterium avium complex infection in mice." Antimicrobial Agents & Chemotherapy. 43. 360-364 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shimizu Tosiaki: "Effects of Chinese traditional medicine Mao-Bushi-saishin-To on therapeutic efficacy of a new benzoxazinorifamycin,KRM-1648,against Mycobacterium avium infection in mice." Antimicrobial Agents & Chemotherapy. (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Sato Katumasa: "Antimicrobial activities of benzoxazinorifamycin (KRM-1648) and clarithromycin against Mycobacterium avium-intracellulare complex residing in murine peritoneal macrophages,human macrophage-like cells and human alveolar epithelial cells." Journal of Antimicrobial Chemotherapy. (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 冨岡 治明: "微生物学 免疫学 (6.抗酸菌, 7.放線菌とノカルジア)" 医学教育出版社, 129-143 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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