KININS AS MEDIATORS OF HUMAN REACTIONS
KININS AS MEDIATORS OF HUMAN REACTIONS
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
中文摘要
缓激肽(BK)是一种有效的促炎性多肽,已被
与鼻炎和哮喘的发病机制有关。尽管
这种多肽在呼吸道疾病中的潜在重要性,
然而,BK在体内发挥作用的机制
人们对航空公司知之甚少。我们已经证明了
患有活动性过敏性疾病的受试者对BK和
这种高反应性是由神经反射调节的,
在无症状受试者的呼吸道中未观察到。出现BK
在这方面是独一无二的。我们可以复制这个
反复定位过敏原实验中的高反应性
挑战。这项建议将结合人体内的研究。
上呼吸道和下呼吸道的体内互补研究
豚鼠模型(其中反射成分可进一步
解剖)进行第一次严格的神经性分析
在过敏性疾病中,对BK的反应会改变,并开始
描述这些过敏性炎症的哪些成分
改变了神经反应。
过敏性炎症可增强对BK的呼吸道反应
或更多的反射路径上的位置。我们将决定
过敏性炎症是否增强了对
BK通过:1)敏化支配
呼吸道粘膜;2)作用于呼吸道传出肢体
副交感神经增加胆碱能和/或损害胆碱能
非胆碱能(NaNC)效应器反应;或3)改变
呼吸道传入活动或改变的中央处理
呼吸道副交感神经节中的突触传递。
我们将确定是否有能力诱导神经
对BK的反应性是过敏的一个独特特征
炎症,通过确定实验性鼻病毒
正常受试者感染也会引起神经高反应性
致BK。根据这些研究的结果,我们将确定
是否应进一步关注炎性成分的作用
以过敏性炎症为特征的(如肥大
细胞/嗜酸性粒细胞产物、选定的细胞因子)在改变中
神经反应或检查其他炎症性疾病
组件。
这些严格的研究不仅将澄清BK在
呼吸道疾病,但也将具有更广泛的相关性
提供了关于神经功能如何的新的和重要的见解
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.
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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
A human lung mast cell chymotrypsin-like enzyme. Identification and partial characterization.
一种人肺肥大细胞胰凝乳蛋白酶样酶。
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
DOI:
10.1016/0002-9343(85)90087-7
发表时间:
1985
期刊:
The American journal of medicine
影响因子:
--
作者:
[Naclerio,RM, Bartenfelder,D, Proud,D, Togias,AG, Meyers,DA, Kagey-Sobotka,A, Norman,PS, Lichtenstein,LM]
通讯作者:
Lichtenstein,LM
共 56 条
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