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Mechamisms of PAF-Induced Airway Hyperresponsiveness in Bronchial Asthma

Research Project

Project/Area Number 62440038
Research Category

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

Allocation TypeSingle-year Grants
Research Field Respiratory organ internal medicine
Research InstitutionDokkyo University School of Medicine

Principal Investigator

MAKINO Sohei  Dokkyo University School of Medicine Professor, 医学部, 教授 (10049140)

Co-Investigator(Kenkyū-buntansha) ARIMA Masahumi  DUSM Fellow, 医学部, 助手 (00202763)
YUKAWA Tatsuo  DUSM Lecturer, 医学部, 講師 (80158336)
MOTOJIMA Shinji  DUSM Lecturer, 医学部, 講師 (90157842)
FUKUDA Takeshi  DUSM Associate Professor, 医学部, 助教授 (90088873)
寺師 義典  獨協医科大学, 医学部, 助手 (90192202)
大塚 智博  獨協医科大学, 医学部, 講師 (10152183)
山田 吾郎  獨協医科大学, 医学部, 講師 (70146174)
山井 孝夫  獨協医科大学, 医学部, 講師 (00182402)
戸田 正夫  獨協医科大学, 医学部, 講師 (50175478)
池森 亨介  獨協医科大学, 医学部, 助教授 (30049176)
Project Period (FY) 1987 – 1990
Project Status Completed (Fiscal Year 1990)
Budget Amount *help
¥14,800,000 (Direct Cost: ¥14,800,000)
Fiscal Year 1990: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1989: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1988: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1987: ¥11,000,000 (Direct Cost: ¥11,000,000)
KeywordsPAF / Eosinophil / Airway hyperresponsiveness / Bronchial asthma / Mouse / Guinea pig / PAF antagonist / Cellular immunity / 好酸球 Eosinophil / 気道過敏性 Airway Hyperresponsiveness / 気管支喘息 bronchial asthma / マウス Mouse / モルモット Guinea pig / PAF拮抗薬(pAF antagonist) / 細胞免疫 cellular immunity / Bronchial asthma / Bronchial responsiveness / Eosinophils / Guinea pig / 血小板活性化因子 / 吸入試験 / 気道収縮 / 実験喘息 / 好酸球浸潤 / 気管支喘 / 気道過敏 / 気道収縮部位
Research Abstract

Research Results : (1) Effects of selective RAF antagonist, WEB2086 on late phase airway narrowing and post-latephase airway hyperresponsiveness (AH) : We already found that antigen exposure caused immediate and latephase AN and post latephase AH in actively sensitized guinea pig. In order to know the roles of PAF on these airway responses, we pretreated actively sensitized guinea pigs and challenged the animals with a specific antigen of ovalbumine (OA). Both latephase AN and post-latephase AH were inhibited significantly, suggesting that PAF might play significant roles in-AH observed in atopic asthma patients. (2) Enhanced PAF-induced eosinophilia in actively sensitized mice, but not in not-sensitized animals. In actively sensitized guinea pigs the inhalation of a specific antigen causes eosinophil infiltration in the bronchial mucosa which last as long as 5 days, while such prolonged eosinophilia is not observed in passively sensitized guinea pig. Since one of the difference of actively sensitized guinea pigs as compared to passively sensitized animals, is the presence of sensitized T-lymphocytes which may activate and prolong the survival of eosinophils. In order to study the role of active sensitization on PAF-induced eosinophil chemotaxis, BALB/C mice were sensitized by intraperitra injection of OA and challenged with intradermal PAF (long/site). Eosinophil infiltration in the skin was measured 6 hours after the intradermal PAF injection 0 and 15 as found that the infiltration was higher in actively sensitized mice as compared to not-sensitized normal mice. These observations suggest that PAF-induced eosinophil infiltration was enhanced possible T-cell derives cytokine, including IL-5. These observation shows possible clinical appreciation of PAF antagonist and suppressing agents in T-cell functions in the treatment of chronic asthma.

Report

(5 results)
  • 1990 Annual Research Report   Final Research Report Summary
  • 1989 Annual Research Report
  • 1988 Annual Research Report
  • 1987 Annual Research Report
  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] 福田 健,阿久津 郁夫,天下井 正弘,沼尾 利郎,本島 新司,牧野 荘平: "モルモット喘息モデルでの2相性好酸球浸潤に対する PAF拮抗剤とCyclosporin Aの効果" アレルギ-. 39(6). 548-552 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 阿久津 郁夫,福田 健,沼尾 利郎,牧野 荘平: "モルモット実験喘息モデルにおける遅発型喘息反応の出現と気道反応性亢進のFKー506による抑制" アレルギ-. 39(7). 605-609 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 有馬 雅史,湯川 龍雄,寺師 義典,相良 博典,牧野 荘平: "モルモット実験喘息モデルにおける遅発型反応と気道過敏性亢進に及ぼすWEB2086の影響" アレルギ-. 40(2). 141-146 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Makino,S.,Fukuda,T.,Motojima,S.,Yukawa,T.: "Eosinophils in aivway hyperresponsiveness,in Inflamatory cells and Mediators in bronchial asthma" CRC Press, 18-249 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Fukuda, T., Akutsu, I., Amagai, M., Numao, T, Motijima, S., Makino, S.: "Antigen-induced biphasic eosinophil infiltration in the airways of actively sensitized guinea pigs and its inhibition by PAF antagonist and cyclosporin A" Jpn. Allergology. 39. 548-552 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Akutsu, I., Fukuda, T., Numao, T., Makino, S.: "Inhibitory effect of FK-506 on the development of late asthmatic response and on the incereased bronchial responsiveness" Jpn. Allergology. 39. 605-609 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Arima, M., Yukawa, T., Terashi, Y., Sagara, H., Makino, S.: "Involvement of platelet activating factor (PAF) in ovalbumin antigen-induced late asthmatic response and increase of airway hyperresponsiveness in a guinea pig experimental model of asthma" Jpn. Allergology. 40. 141-146 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 福田 健,阿久津 郁夫,犬下井 正弘,沼尾 利郎,本島 新司,牧野 荘平: "モルモット喘息モデルでの2相性好酸球浸潤に対するPAF拮抗剤とCyclosporin Aの効果" アレルギ-. 39(6). 548-552 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 阿久津 郁夫,福田 健,沼尾 利郎,牧野 荘平: "モルモット実験喘息モデルにおける遅発型喘息反応の出現と気道反応性亢進のFKー506による抑制" アレルギ-. 39(7). 605-609 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 有馬 雅史,湯川 龍雄,寺師 義典,相良 博典,牧野 荘平: "モルモット実験喘息モデルにおける遅発型反応と気道過敏性亢進に及ぼすWEB2086の影響" アレルギ-. 40(2). 141-146 (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Makino,S.,Fukuda,T.,Motojima,S.Yukawa,T.: "Eosinophits in airway hyperresponsiveness,in Inflamatory cells and Mediators in brochial asthma" CRC Press, 18/249 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 有馬雅史,山田吾郎,福田健,牧野荘平: "健常者および気管支喘息患者におけるPAF吸入の中枢気道と末梢気道に対する影響の検討" アレルギ-. 38. 194 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Goro Yamada,Sohei Makino: "Airway responsis to inhaled PAF(Platelet-Activating Factor)in nomal guinea pigs" Lipids Submitted for publication.

    • Related Report
      1989 Annual Research Report
  • [Publications] 福田健,阿久津郁夫,沼尾利郎,牧野荘平: "好酸球" 現代化学 血小板活性化因子ー生化学・生理・病理ー. 17. 109-121 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 牧野荘平,福田健,山田吾郎: "気管支喘息" 現代化学 血小板活性化因子ー生化学・生理・病理ー. 17. 171-178 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 山田吾郎,牧野荘平: "気管支喘息におけるPAFの役割" 日本炎症学会(第9回)プログラム集. 87 (1988)

    • Related Report
      1989 Annual Research Report
  • [Publications] T.Fukuda,T.Numao,G.Yamada and S.Makino: "PAF IN ASTHMA" Edited by G.Holme and J.Morley Academic Press(London), 219-228 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] G.Yamada,S.Watanabe,T.Fukuda and S.Makino: "PAF IN ASTHMA" Edited by G.Holme and J.Morley Academic Press(London), 231-238 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 山田吾郎,牧野荘平: 第9回日本炎症学会誌. 87 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] GYAMADA;S.WATANABE;A.HIRATA;T.OTSUKA;T.YAMAI;S.MAKINO: Allergy Proceeding. 325 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 有馬雅史,山田吾郎,福田健,牧野荘平: 春季アレルギー学会発表予定(1989). (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] Y.TERASHI, T.YUKAWA, K.TERASHI, S.MOTOJIMA, K.FUKUDA, S.MAKINO: THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. 81. 194 (1988)

    • Related Report
      1987 Annual Research Report
  • [Publications] T.FUKUDA, T.NUMAO, I.AKUTSU, S.MOTOJIMA, S.MAKINO: THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. 81. 206 (1988)

    • Related Report
      1987 Annual Research Report

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Published: 1987-04-01   Modified: 2016-04-21  

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