| Project/Area Number |
62440038
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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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 | Dokkyo University School of Medicine |
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Principal Investigator |
MAKINO Sohei Dokkyo University School of Medicine Professor, 医学部, 教授 (10049140)
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| Co-Investigator(Kenkyū-buntansha) |
ARIMA Masahumi DUSM Fellow, 医学部, 助手 (00202763)
YUKAWA Tatsuo DUSM Lecturer, 医学部, 講師 (80158336)
MOTOJIMA Shinji DUSM Lecturer, 医学部, 講師 (90157842)
FUKUDA Takeshi DUSM Associate Professor, 医学部, 助教授 (90088873)
寺師 義典 獨協医科大学, 医学部, 助手 (90192202)
大塚 智博 獨協医科大学, 医学部, 講師 (10152183)
山田 吾郎 獨協医科大学, 医学部, 講師 (70146174)
山井 孝夫 獨協医科大学, 医学部, 講師 (00182402)
戸田 正夫 獨協医科大学, 医学部, 講師 (50175478)
池森 亨介 獨協医科大学, 医学部, 助教授 (30049176)
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| Project Period (FY) |
1987 – 1990
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| Project Status |
Completed (Fiscal Year 1990)
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| Budget Amount *help |
¥14,800,000 (Direct Cost: ¥14,800,000)
Fiscal Year 1990: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1989: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1988: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1987: ¥11,000,000 (Direct Cost: ¥11,000,000)
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| Keywords | PAF / Eosinophil / Airway hyperresponsiveness / Bronchial asthma / Mouse / Guinea pig / PAF antagonist / Cellular immunity / 好酸球 Eosinophil / 気道過敏性 Airway Hyperresponsiveness / 気管支喘息 bronchial asthma / マウス Mouse / モルモット Guinea pig / PAF拮抗薬(pAF antagonist) / 細胞免疫 cellular immunity / Bronchial asthma / Bronchial responsiveness / Eosinophils / Guinea pig / 血小板活性化因子 / 吸入試験 / 気道収縮 / 実験喘息 / 好酸球浸潤 / 気管支喘 / 気道過敏 / 気道収縮部位 |
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| Research Abstract |
Research Results : (1) Effects of selective RAF antagonist, WEB2086 on late phase airway narrowing and post-latephase airway hyperresponsiveness (AH) : We already found that antigen exposure caused immediate and latephase AN and post latephase AH in actively sensitized guinea pig. In order to know the roles of PAF on these airway responses, we pretreated actively sensitized guinea pigs and challenged the animals with a specific antigen of ovalbumine (OA). Both latephase AN and post-latephase AH were inhibited significantly, suggesting that PAF might play significant roles in-AH observed in atopic asthma patients. (2) Enhanced PAF-induced eosinophilia in actively sensitized mice, but not in not-sensitized animals. In actively sensitized guinea pigs the inhalation of a specific antigen causes eosinophil infiltration in the bronchial mucosa which last as long as 5 days, while such prolonged eosinophilia is not observed in passively sensitized guinea pig. Since one of the difference of actively sensitized guinea pigs as compared to passively sensitized animals, is the presence of sensitized T-lymphocytes which may activate and prolong the survival of eosinophils. In order to study the role of active sensitization on PAF-induced eosinophil chemotaxis, BALB/C mice were sensitized by intraperitra injection of OA and challenged with intradermal PAF (long/site). Eosinophil infiltration in the skin was measured 6 hours after the intradermal PAF injection 0 and 15 as found that the infiltration was higher in actively sensitized mice as compared to not-sensitized normal mice. These observations suggest that PAF-induced eosinophil infiltration was enhanced possible T-cell derives cytokine, including IL-5. These observation shows possible clinical appreciation of PAF antagonist and suppressing agents in T-cell functions in the treatment of chronic asthma.
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