Project/Area Number |
12670553
|
Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Respiratory organ internal medicine
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Research Institution | TOKYO MEDICAL & DENTAL UNIVERSITY |
Principal Investigator |
MIYAKE Shuji TOKYO MEDICAL & DENTAL UNIVERSITY, THE PULMONARY MEDICINE, ASSISTANT ADJUNCT PROFESSOR, 大学院・医歯学総合研究科, 助手 (50239365)
|
Project Period (FY) |
2000 – 2001
|
Project Status |
Completed (Fiscal Year 2001)
|
Budget Amount *help |
¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2001: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2000: ¥600,000 (Direct Cost: ¥600,000)
|
Keywords | bird fancier's lung / pulmonary fibrosis / pigeon dropping extracts / cytokine / TNFα / IFNγ / IL-10 / IL-10 / 鳩飼病 / 過敏性肺炎 |
Research Abstract |
Hypersensitivity pneumonitis (HP) is a lung disease caused by sensitization to and repeated inhalation of various organic antigens. One form of HP, known as bird fancier's lung (BFL) is a form of extrinsic allergic alveolitis (EAA) caused by hypersensitivity reactions to inhaled pigeon antigens in the lung of a sensitized host. The clinical manifestation of BFL is not uniform and the etiology of the clinical variety is under investigation. To alleviate the difficulties in clarifying the etiology, an animal model of BFL was developed in mice. Instilling pigeon dropping extracts (PDE) in saline intranasally three times a week for more than 4 weeks induced hypersensitivity pneumonitis. Repeated intranasal sensitization with PDE caused significant increase of lung/body weight ratio, increase of BAL cell counts with transient neutrophil increase, and dense accumulation of lymphocytes around the bronchovascular region. Production of anti PDE antibody was observed and sensitization with PDE mo
… More
re than 8 μg for 4 weeks caused comparable pulmonary changes. Extended sensitization with PDE (17 weeks) caused more prominent increase of lung/body weight ratio than that of the 4-week sensitized group and induced the alveolar lesion characterized by filling of the alveoli mainly with increased numbers of alveolar macrophages and the mild alveolar thickening by infiltrates with mononuclear cells in addition to the peribronchiolar and perivascular inflammation. Sensitization with PDE for 4 weeks did not result in significant increase of hydroxyproline but that for 17 weeks caused significant increase in contents of hydroxyproline in right lungs suggesting the extended sensitization with PDE might induce pulmonary fibrotic changes that were not observed in 4week sensitization with PDE. The real time quantitative PCR values of IL-10, TNFα, and IFNγ mRNA in left whole lungs were increased by the sensitization with PDE in both groups but expression of IL-2, IL-5, IL-6 and IL-12 mRNA in left whole lungs was not changed by the intranasal sensitization with PDE for 4 weeks and 17 weeks. These results suggest the significance of these pro-inflammatory cytokines and anti-inflammatory cytokine in hypersensitivity pneumonitis induced by PDE. Less
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