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KININS AS MEDIATORS OF HUMAN REACTIONS

KININS AS MEDIATORS OF HUMAN REACTIONS
激肽作为人类反应的调节剂
批准号:
6637448
负责人:
BRENDAN J CANNING
金额:
$14.3万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1988
资助国家:
美国
项目状态:
已结题
起止时间:
1988-09-12 至 2003-09-30

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项目成果

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中文摘要
翻译
缓激肽(BK)是一种有效的促炎肽, 与鼻炎和哮喘的发病机制有关。 尽管 这种肽在气道疾病中的潜在重要性, 然而,BK发挥其作用的机制, 对气道了解甚少。 我们已经证明, 患有活动性变态反应性疾病的受试者对BK反应过度, 这种高反应性是由神经反射介导的, 在无症状受试者的气道中未观察到。 BK出现 在这方面独一无二。 我们可以复制这个 使用重复定位变应原的实验性高反应性 挑战. 该建议将联合收割机与人体内研究相结合 上和下气道,并在体内进行补充研究 豚鼠模型(其中反射成分可以进一步 解剖)进行第一次严格的分析,如何神经 在过敏性疾病中,对BK的反应发生改变,并且开始 描述这些过敏性炎症的组成部分 改变了神经反应 过敏性炎症可增强气道对BK的反应, 或沿反射路径的沿着多个位点。 我们将确定 过敏性炎症是否会增强气道对 BK通过:1)使支配大脑皮层的传入神经末梢敏感, 2)作用于气道的传出支 副交感神经增加胆碱能和/或损害 非胆碱能(NANC)效应子应答;或3)改变 中枢处理气道传入活动或改变 气道副交感神经节突触传递。 我们将确定是否有能力诱导神经 对BK的反应性是过敏性 通过确定实验性鼻病毒 正常受试者的感染也诱导神经高反应性 根据这些研究的结果,我们将确定 是否进一步关注炎症成分的作用 过敏性炎症的特征(例如肥大细胞) 细胞/嗜酸性粒细胞产物,选择的细胞因子)的改变 神经反应或检查其他炎症 件. 这些严格的研究不仅将阐明BK在 呼吸道疾病,但也将有更广泛的相关性, 提供了新的和重要的见解,神经功能是如何 在哮喘和鼻炎中发生改变。
英文摘要
Bradykinin (BK) is a potent proinflammatory peptide that has been implicated in the pathogenesis of rhinitis and asthma. Despite the potential importance of this peptide in airway diseases, however, the mechanisms by which BK exerts its effects in the airways are poorly understood. We have shown that the airways of subjects with active allergic disease are hyperreactive to BK and that this hyperreactivity is mediated by neural reflexes that are not observed in the airways of asymptomatic subjects. BK appears to be unique in this regard. We can reproduce this hyperreactivity experimentally using repeated localized allergen challenge. This proposal will combine in vivo studies in human upper and lower airways with complementary studies in an in vivo guinea pig model (in which reflex components can be further dissected) to perform the first rigorous analysis of how neural responses to BK are altered in allergic disease, and to begin to delineate which components of allergic inflammation underly these altered neural responses. Allergic inflammation could enhance airway responses to BK at one or more sites along the reflex pathway. We will determine whether allergic inflammation enhances airway responsiveness to BK by: 1) sensitizing afferent nerve terminals innervating the airway mucosa; 2) acting on the efferent limb of airway parasympathetic nerves to increase cholinergic and/or impair noncholinergic (NANC) effector responses; or 3) altering the central processing of airway afferent activity or altering synaptic transmission in airway parasympathetic ganglia. We will establish whether the ability to induce neural responsiveness to BK is a unique feature of allergic inflammation, by determining whether experimental rhinovirus infection of normal subjects also induces neural hyperreactivity to BK. Based on the results of such studies, we will determine whether to focus further on the role of inflammatory components that are characteristic of allergic inflammation (e.g. mast cell/eosinophil products, selected cytokines) in the alteration of neural responsiveness or to examine other inflammatory components. These rigorous studies will not only clarify the role of BK in airway diseases, but will also have broader relevance by providing new and important insights into how neural function is altered in asthma and rhinitis.
期刊论文(89)
专著(0)
科研奖励(0)
会议论文
Observations on nasal late phase reactions.
鼻腔晚相反应的观察。
DOI: 10.3109/08820138709087108
发表时间: 1987
期刊: Immunological investigations
影响因子: 2.8
作者: [Naclerio,RM, Kagey-Sobotka,A, Lichtenstein,LM, Togias,AG, Iliopoulos,O, Pipkorn,U, Bascom,R, Norman,PS, Proud,D]
通讯作者: Proud,D
DOI: 10.1172/jci112276
发表时间: 1986
期刊: The Journal of clinical investigation
影响因子: --
作者: [Wintroub,BU, Kaempfer,CE, Schechter,NM, Proud,D]
通讯作者: Proud,D
DOI: --
发表时间: 1989-12
期刊: Annals of allergy
影响因子: --
作者: [F. Baroody;D. Proud;A. Kagey-sobotka;L. Freidhoff;P. Norman;L. Lichtenstein;R. Naclerio]
通讯作者: F. Baroody;D. Proud;A. Kagey-sobotka;L. Freidhoff;P. Norman;L. Lichtenstein;R. Naclerio
Kinins in the pathogenesis of human airway diseases.
激肽在人类气道疾病发病机制中的作用。
DOI: --
发表时间: 1994
期刊: Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas
影响因子: --
作者: [Proud,D]
通讯作者: Proud,D
56
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    • 批准号:
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    • 项目类别:
    • 资助金额:
      $51.53万
    • 财政年份:
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    • 负责人:
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    • 依托单位:
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    • 项目类别:
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    • 项目类别:
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    • 负责人:
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    • 依托单位:
    Pilot Study of Zinc Acetate for Chronic Cough
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    • 项目类别:
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    • 财政年份:
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