| Project/Area Number |
07670663
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | SHINSHU UNIVERSITY SCHOOL OF MEDICINE |
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Principal Investigator |
HONDA Takayuki (1996) SHINSHU UNIV.SCH.OF MED.ASSISTANT PROFESSOR, 医学部・附属病院, 講師 (80238815)
藤本 圭作 (1995) 信州大学, 医学部・附属病院, 助手 (70242691)
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| Co-Investigator(Kenkyū-buntansha) |
FUJIMOTO Keisaku SHINSHU UNIV.SCH.OF MED.ASSISTANT, 医学部・附属病院, 助手 (70242691)
KUBO Keishi SHINSHU UNIV.SCH.OF MED.ASSISTANT PROFESSOR, 医学部, 講師 (80143965)
KOBAYASHI Toshio SHINSHU UNIV.SCH.OF MED.ASSISTANT PROFESSOR, 医学部・附属病院, 講師 (80020775)
本田 孝行 信州大学, 医学部・附属病院, 講師 (80238815)
酒井 秋男 信州大学, 医学部・スポーツ医学部野, 助教授 (70020758)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1996: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1995: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Bronchial asthma / Antigen-induced asthmatic response / Eosinophil / Lipid peroxidation / Ascaris-sensitized sheep / Airway hyperreactivity / Induced sputum / Eosinophil cationic protein / 緬羊 / 即時型喘息反応 / 遅発型喘息反応 / ECP / 遅発型の喘息反応 / U74006F / TAK-225 |
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| Research Abstract |
The inhaled provocation of Ascaris antigen to naturally sensitized sheep induced both immediate asthmatic response (IAR) and late asthmatic response (LAR) in about 67% of all sensitized sheep, however, the rest showed only IAR.The dual respondent sheep also showed an significant increased airway reactivity to methacholine and recruitment of neutrophils and eosinophils into the airway 8 hour after the provocation, whereas the single respondent sheep showed a slight increase in airway reactivity and neutrophils recruitment alone. The pretreatment with the inhibitor of lipid peroxidation, U-74006F,and the inhibitor of eosinophil chemotactic activity, TAK-225, significantly reduced antigen-induced asthmatic responses, especially LAR together with the inhibition of eosinophil recruitment into the airway in dual respondent sheep. The pretreatment of TAK-225 also inhibited the development to airway hyperreactivity (AHR). These findings suggest that lipid peroxidation is involved in antigen-induced asthmatic responses and eosinophil recruitment into the airway, and that the accumulated eosinophils contribute to the development of LAR and AHR.In order to examine the involvement of eosinophils clinically, we analyzed the inflammatory cell populations and biochemical substances in induced sputum from mild to severe asthmatics (n=36). The eosinophil numbers and eosinophil cationic protein (ECP) levels were significantly increased in accordance with the severity of asthma, and the ECP levels were significantly positively correlated with the symptom score and negatively correlated with the airflow obstruction. These findings suggest that the eosinophil activation in the airway is closely linked to the symptoms and airflow obstruction of asthma.
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