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Experimental Studies on Mechanisms of Eosinophil Infiltration in Airways in Bronchial Asthma and on its Modulation by Drugs

Research Project

Project/Area Number 62570351
Research Category

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

Allocation TypeSingle-year Grants
Research Field Respiratory organ internal medicine
Research InstitutionDokkyo Medical University

Principal Investigator

FUKUDA Takeshi  Dokkyo University School of Medicine (DUSM), Associate Professor, 医学部, 助教授 (90088873)

Co-Investigator(Kenkyū-buntansha) AKUTSU Ikuo  DUSM, Fellow, 医学部, 助手 (90184126)
NUMAO Toshio  DUSM, Fellow, 医学部, 助手 (60172748)
YAMADA Goro  DUSM, Lecturer, 医学部, 講師 (70146174)
Project Period (FY) 1987 – 1989
Project Status Completed (Fiscal Year 1990)
Budget Amount *help
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1989: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1988: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1987: ¥600,000 (Direct Cost: ¥600,000)
KeywordsBronchial asthma / Eosinophil infiltration / Guinea pig / Experimental model of asthma factor / Eosinophil chemotactic / Platelet-activating factor / T-cell / Lymphokine / 好酸球 / 好中球 / PAF / 炎症細胞浸潤 / 遊走 / 卵白アルブミン
Research Abstract

There is now considerable evidence that eosinophils participate in the sathma process as proinflammatory effector cells, and recent attention has been focused on the mechanisms of airway eosinophil accumulation in ongoing disease. This study was dedigned to determine which mediators are actually responsible for attracting eosinophils to the airway mucosa and examine the effect of suppression of airway eosinophilia on the pathophysiology of asthma. Guinea pigs sensitized by intraperitoneal injection of ovalbumin (OA) responded to a single exposure to aerosolized OA with biphasic infiltration of eosinophils in the airways ; a striking early-phase which peaked at 6 hr and a delayed-phase which peaked at 24 hr and persisted for as long as 5 days. The early-phase infiltration was suppressed by the precious administration ofPAF antagonist, and the delayed-phase was inhibited when animals were treated with Cyclosporin A (CyA) or FK-506 (FK), T lymphocyte-selective immunosuppressive agents. Th … More ese results suggested that PAF may contribute to early-phase and T cell factor (s) may contribute to delayed-phase eosinophil infiltration of the airways. To look at whether PAF generation really occurs in the lungs of guinea pigs after antigen challenge, we determined PAF activity in bronchoalveolar lavage (BAL) fluids and found that there existedl pmol of PAF ler 1 kg body weight. Suppression of airway eosinophilia by CyA and FK resulted in the inhivition of antigen-induced late asthmatic response and a subsequent increase in bronchial hyperresponsiveness in guineapigs immunized by repeated exposure to aerosolized OA, raising the possibility that drugs precenting eosinophil migration into the airways would be useful in the treatment of asthma.
Finally, we tested whether PAF- or lymphokine-like substance might be also important in the antigeninduced eosinophil infiltration in humans. Basophils and mononuclear cells were separated from the peripheral blood of Dermatophagoides farinae (DF) -sensitive asthmatic subjects, cultured in the presence of DF antigen and eosinophil chemotactic activity (ECA) in the supernatants was tested using a modified Boyden chamber technique. Basophils produced ECA which was blocked by a specific PAF antagonist, whereas mononuclear cells produced heat-stable ECA with a MW 30,000, presumably lymphokine, which peaked at 3-5 day. These results suggest that PAF- and lymphokine-like substance may play a key role in the airway eosinophils in asthmatic subjects. Less

Report

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

    (34 results)

All Other

All Publications (34 results)

  • [Publications] 福田 健,阿久津 郁夫,沼尾 利郎,本島 新司,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の発現を気道反応性亢進のCyclosprinAによる抑制" アレルギ-. 39. 483-487 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [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CyclosporinAの効果" アレルギ-. 39. 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. 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] 福田 健,阿久津 郁夫,中島 宏和,福島 康次,沼尾 利郎,安東 直彦,本島 新司,牧野 荘平: "モルモット喘息モデルの気道反応性亢進における好酸球,好中球、リンパ球の役割" 日本胸部疾患学会雑誌. 28. 1228-1293 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 福島 康次,福田 健,牧野 荘平: "気管支喘息患者におけるダニ抗原刺激による末梢血単核球培養上清中の好酸球遊走活性の検討" アレルギ-. 40. 108-116 (1991)

    • 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.,Motojima,S.,Makino,S.: "Inhibition of antigenーinduced late asthmatic response and bronchial hyperresponsiveness by Cyclosporin and FK506" Int Arch Allergy Appl Immunol.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 福田 健,湯川 龍雄,寺師 義典,阿久津 郁夫,本島 新司,牧野 荘平: "宮本昭正編 デ-・エム・ベ-・ジャパン" 第7回免疫薬理シンポジウム. 53-58 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 沼尾 利郎,福田 健,阿久津 郁夫,中島 宏和,牧野 荘平,榎原 英夫: "宮本昭正編 デ-・エム・ベ-・ジャパン" 第7回免疫薬理シンポジウム. 101-108 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 福田 健,阿久津 郁夫,福島 康次,本島 新司,牧野 荘平: "牧野荘平編 デ-・エム・ベ・ジャパン" 第8回免疫薬理シンポジウム.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 福田 健,牧野 荘平: "ライフサンエンス" PAFーRVAー,ケミカルディエ-タ-の生物学的意義.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 福田 健,沼尾 利郎,阿久津 郁夫 本島 新司,牧野 荘平: "第5回免疫薬理シンポジウム" デ-・エム・ベ-・ジャパン, 59-72 (1987)

    • 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.,Numao,T.,Motojima,S.: "Triangle" 103-112 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Fukuda, T.: "Inhibition of antigen-induced late asthamtic response and bronchial hyper responsiveness by Cyclosporin A." Jpn. J. Allergol.39. 483-487 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Fukuda, T.: "Antigen-induced biphasic eosinophil infilt-ration-in the airways of actively sensitized guinea pigs and its inhibition by PAF antagonist and Cyclosporin A" Jpn. J. Allergol.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.: "Inhibitory effect of FK-506 on the development of late asthmatic response and on the increased bronchial responsiveness." Jpn. J. Allergol. 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] Fukuda, T.: "The role of eosinophils, neutrophils and lymphocytes for the development of bronchial hyperresponsiveness in a guinea pig model of asthma" Jpn. J. Thorac. Dis.28. 1288-1293 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Fukushima, Y.: "Eosinophil chemotactic activity in the supernatant of mononuclear cell culture stimulated with specific antigen" Jpn. J : Allergol.40. 108-116 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Fukuda, T.: "Inhibition of antigen-induced late asthmatic response and bronchial hyperresponsiveness by ciclosporin and FK506" Int. Arch. Allergy Appl. Immunol.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Fukuda, T.: "Eosinophil chemotactic mediators in type I allergic reaction." The Proceeding of the 5th symposium of immunopharmacology. 59-72 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Fukuda, T.: "The eosinophil in asthma" Triangle. 27. 103-112 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Fukuda, T.: "Different bronchial responses to aerosolized antigen in guinea pigs sensitized with different administration route" The proceeding of the 7th symposium of immunopharmacology. 53-58 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Numao, T.: "Selective enhancement of PAF-induced human eosinophil chemotaxis by recombinant human interleukin-5" The proceeding of the 7th symposium of immunopharmacology. 101-108 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Fukuda, T.: "Cyclosporin and allergic inflammation in airways" The proceeding of the 8th symposium of immunopharmacology. 93-99 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Fukuda, T.: "Paf-RIA-" Biological significance of chemical mediators Life Science.

    • 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,天下井正弘,沼尾利郎,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拮抗薬とCyclosporin Aの効果" アレルギ-.

    • Related Report
      1989 Annual Research Report
  • [Publications] 福田健,阿久津郁夫,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発現と気道反応性亢進のCyclosporin Aによる抑制" アレルギ-.

    • Related Report
      1989 Annual Research Report
  • [Publications] 福田健,湯川龍雄,寺師義典,阿久津郁夫,本島新司,牧野荘平: "感作経路の違いによる抗原吸入チャレンジ後の気道反応の相違" 第7回 免疫薬理シンポジウム記録集. 53-60 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Akutsu,I.,fukuda,T.,Numao,T.,Makino,S.: "Contribution of T cell factor(s)to delayed-phase cosinophil accumulation in the airway mucosa of actively-sensitized guinea pigs." J.Allergy Clin,Immunol.85. 234 (1990)

    • Related Report
      1989 Annual Research Report
  • [Publications] Akutsu,I.;Fukada,T.;Amagai,M.;Numao,T.;Makino,S.: J.Allergy Clin.Immunol.83. 273 (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] Fukuda,T.;Numao,T.;Akutsu,I.;Makino,S.: J.Allergy Clin.Immunol.83. 193 (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] Numao,T.;Fukuda,T.;Akutsu,I.;Makino,S.;Enokihara,H.;Honjo,T.: J.Allergy Clin.Immunol.83. 298 (1989)

    • Related Report
      1988 Annual Research Report
  • [Publications] FUKUDA, T.: The Journal of Allergy and Clinical Immunology. 81. 206 (1988)

    • Related Report
      1987 Annual Research Report
  • [Publications] TERASHI, Y.: The Journal of Allergy and Clinical Immunology. 81. 194 (1988)

    • Related Report
      1987 Annual Research Report
  • [Publications] 福田健: 免疫薬理シンポジウム記録集. 5. 59-74 (1987)

    • Related Report
      1987 Annual Research Report

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

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