2002 Fiscal Year Final Research Report Summary
A role of peptide leukotoriene in bronchial asthma
| Project/Area Number |
13670447
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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 |
内科学一般
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| Research Institution | Ochanomizu University |
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Principal Investigator |
MORITA Yutaka Ochanomizu University, Health Care Center, Professor, 保健管理センター, 教授 (60107620)
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| Co-Investigator(Kenkyū-buntansha) |
KOSHINO Takeshi University of Tokyo, Department of Respiratory Medicine, 医学部, 助手 (10282659)
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| Project Period (FY) |
2001 – 2002
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| Keywords | Peptide Leukotriene / eoshinophils |
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| Research Abstract |
Background : The cysteinyl leukotrienes (CysLTs) mediate their biological actions through two receptors : CysLT_1 receptor and CysLT_2 receptor.
Objective : This study was undertaken to examine the direct effects of CysLTs on eosinophils, such as chemotaxis and degranulation, focusing on CysLT_1.
Methods : Eosinophils were isolated from venous blood from normal volunteers who had no history of allergy (purity : > 99%). They were subjected to reverse transcription-PCR analysis and flow cytometric analysis for CysLT_1. Binding assays were performed with [^3H]LTD_4. Purified eosinophils loaded with Fura-2-acetoxymethyl ester was stimulated with CysLTs, and Ca^<2+> influx was measured. Eosinophil migration in response to CysLTs was measured using a 96-well multiwell Boyden chamber. Eosinophils were treated with LTD_4 at 10^<-6> M for 60 min, followed by incubation for 4 h at 37℃ in the presence or absence of IL-5, and EDN release was evaluated.
Results : The expression of the mRNA and protein of CysLT_1 on eosinophils, and [^3H]LTD_4-specific binding to eosinophils, were observed. Neither Th1 cytokine (IFN-g) nor Th2 cytokines (IL-4 or IL-5) affected CysLT_1 expression in eosinophils. CysLTs induced an increase in intracellular free Ca^<2+> in eosinophils via CysLT_1, as suggested by the efficient inhibition by a CysLT_1 antagonist, pranlukast, in addition to the rank order of potency being LTD_4, LTC_4, and LTE_4. LTD_4 stimulated eosinophils to migrate at 10^<-6> M via CysLT_1. LTE_4 also induced significant eosinophil migration at 10^<-6> M. LTD_4 enhanced EDN release induced by IL-5 via CysLT_1.
Conclusion : CysLTs induce migration and enhance degranulation in eosinophils via CysLT_1. Accordingly, interaction of CysLTs and CysLT_1 on eosinophils has potential to play a prominent role in the pathophysiology of asthma.
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Research Products
(2 results)
