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The Pathogenesis of Emphysema- Alpha-1 Antitrypsin Dysfunction Induced by Triggered Neutrophils and Alveolar Macrophages-

Research Project

Project/Area Number 61480197
Research Category

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

Allocation TypeSingle-year Grants
Research Field Respiratory organ internal medicine
Research InstitutionSaga Medical School

Principal Investigator

YAMADA HOZUMI  Associate professor, Internal Medicine, Saga Medical School, 医学部, 助教授 (70117282)

Co-Investigator(Kenkyū-buntansha) KATOH OSAMU  Asistant professor, Internal Medicine, Saga Medical School, 医学部, 講師 (90152701)
Project Period (FY) 1986 – 1987
Project Status Completed (Fiscal Year 1987)
Budget Amount *help
¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 1987: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1986: ¥4,000,000 (Direct Cost: ¥4,000,000)
KeywordsNeutrophil / Alpha-1 Antitrypsin / EIC / TIC / BALF / BALF / エラスターゼ活性 / 【α_1】-アンチトリプシン
Research Abstract

This study was done to discuss the pathogenesis of emphysema. There has been a progeinase-antiproteinase balance hypothesis for the pathogenesis of emphysema. Many investigetors showed experimental models of emphysema induced by neutrophil elastase, and also demonstrated the antiproteinase dysfunction in the bronchoalveolar lavage fluid (BALF) from smokers, pneumonia patients and adult respiratory distress syndrome patients. In this study, we determined both elastase activity and antiproteinase activity in BALF in order to declare the proteinase-antiproteinase imbalance in the lung tissues. Firstly, we demonstrated that BALF from patients with chronic respiratory tract infections showed high elastase activity. It was revealed that the elastase in BALF was a serine proteinase and its source might be neutrophils. Secondary, alpha-1 antitrypsin <alpha>_1AT) in BALF was inactivated functionally either in smokers or in patients with chronic respiratory tract infections. These data suggest that neutrophil elastase is most important proteinase which injures lung tissues, and that either infection or smoking reduces elastase inhibitory capacity of the local <alpha>_1At. On the other hand, in vitro study, we demonstrated the <alpha>_1AT dysfunction induced by triggered neutrophils, and showed that the mechanisms of this dysfunction was attributed to <alpha>_1AT oxidation by oxgen products from neutrophils. This study suggest that either the increase of neutrophil elastase activity or the reduction of <alpha>_1AT function in the lung tissues produces the proteinase- antiproteinase imalance, which may result in the development of emphysema.

Report

(2 results)
  • 1987 Final Research Report Summary
  • 1986 Annual Research Report
  • Research Products

    (11 results)

All Other

All Publications (11 results)

  • [Publications] 山田穂積: 日本胸部疾患学会誌. 26. 57-63 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] 山田穂積: 日本気管支学会誌.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] 山田穂積: 日本胸部疾患学会誌.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] HOZUMI YAMADA: Am. J. Pathol.109. 145-156 (1982)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Hozumi Yamada: Am. Rev. Respir. Dis.125. 226 (1981)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] WILLIAM R. ABRAMS: Am. Rev. Respir, Dis.129. 735-741 (1984)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Hozumi Yamada: "Elastase Activity in Bronchoalveolar Lavage Fluid from Patients with Chronic Respiratory Tract Infections" Jap. J. Thoracic Dis.26. 57-63 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Hozumi Yamada: "The Pathogenesis of Emphysema. -Alpha-1 Antitrypsin Dysfunction Induced by Triggered Neutrophils-" Jap. J. thoracic Dis.(1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Hozumi Yamada: "A Study of Alpha-1 Antitrypsin Function in BALF from Smokers and Nonsmokers" J. Jap. Soc. Bronchology. (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Hozumi Yamada: "Acute Experimental Pulmonary Inflammation; Neutrophil Degranulation and Tissue Damage" Am. Rev. Respir. Dis.125. 226 (1981)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Hozumi Yamada: "Neutrophil Degranulation in Cadmium-Chloride-Induced Acute Lung Inflammation" Am. J. Pathol.109. 145-156 (1982)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary

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Published: 1987-03-31   Modified: 2016-04-21  

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