The Pathogenesis of Emphysema- Alpha-1 Antitrypsin Dysfunction Induced by Triggered Neutrophils and Alveolar Macrophages-
| Project/Area Number |
61480197
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Saga Medical School |
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Principal Investigator |
YAMADA HOZUMI Associate professor, Internal Medicine, Saga Medical School, 医学部, 助教授 (70117282)
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| Co-Investigator(Kenkyū-buntansha) |
KATOH OSAMU Asistant professor, Internal Medicine, Saga Medical School, 医学部, 講師 (90152701)
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| Project Period (FY) |
1986 – 1987
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| Project Status |
Completed (Fiscal Year 1987)
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| 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)
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| Keywords | Neutrophil / 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 |
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| 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.
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Report
(2 results)
Research Products
(11 results)
