1990 Fiscal Year Final Research Report Summary
Mechamisms of PAF-Induced Airway Hyperresponsiveness in Bronchial Asthma
| 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)
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| Project Period (FY) |
1987 – 1990
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| Keywords | PAF / Eosinophil / Airway hyperresponsiveness / Bronchial asthma / Mouse / Guinea pig / PAF antagonist / Cellular immunity |
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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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[Publications] Fukuda, T., Akutsu, I., Amagai, M., Numao, T, Motijima, S., Makino, S.: "Antigen-induced biphasic eosinophil infiltration in the airways of actively sensitized guinea pigs and its inhibition by PAF antagonist and cyclosporin A" Jpn. Allergology. 39. 548-552 (1990)
Description
「研究成果報告書概要(欧文)」より
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