Incubation with IgE increases cholinergic neurotransmission in human airways in vitro
Incubation with IgE increases cholinergic neurotransmission in human airways in vitro
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DOI：
10.1164/ajrccm.154.5.8912735
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发表时间：
1996-11-01
影响因子：
24.7
通讯作者：
Shirato, K
中科院分区：
文献类型：
--
作者：
Ichinose, M;Miura, M;Shirato, K
哮喘患者气道胆碱能高反应性是常见的现象。最近的报告表明，IgE可能参与高反应性，虽然确切的机制仍然不确定。在这项研究中，我们探讨了与IgE孵育是否可以促进人类气道中的胆碱能功能。支气管取自20例肺切除患者。分别用电场刺激（EFS）和外源性乙酰胆碱（ACh）诱发豚鼠离体心脏的胆碱能收缩反应，并通过等长收缩张力测定来评价。高效液相色谱法测定了EFS诱导的胆碱能神经ACh释放。与热灭活IgE孵育的支气管相比，IgE孵育显著增强了EFS诱导的支气管收缩和ACh释放（分别为p < 0.05），但不改变外源性ACh诱导的收缩反应。在对照组织中，用毒蕈碱M（2）受体激动剂毛果芸香碱预处理可减少EFS诱导的ACh释放（p < 0.05），但在IgE孵育的组织中则不然。M（2）-受体拮抗剂methoctramine显著增强对照支气管中EFS诱导的收缩（p < 0.05），但在与IgE孵育的组织中未观察到这种增强。这些结果表明，IgE本身可以通过促进胆碱能神经释放ACh来增强胆碱能支气管收缩，这种增强作用与神经末梢自身受体M（2）功能障碍有关。
Airway cholinergic hyperresponsiveness is frequently observed in asthmatic patients. Recent reports suggest the possible involvement of IgE in hyperresponsiveness, although the exact mechanism is still uncertain. In this study, we era mined whether incubation with IgE could facilitate the cholinergic function in human airways. Bronchi were obtained from 20 patients undergoing lung resection. Cholinergic contractile responses were induced by electrical field stimulation (EFS) or exogenous acetylcholine (ACh), and they were assessed by isometric tension measurement. EFS-induced ACh release from cholinergic nerves was also measured by high performance liquid chromatography. Incubation with IgE significantly enhanced EFS-induced bronchial contraction and ACh release as compared with the values of the bronchi incubated with heat inactivated IgE (control) (p < 0.05, respectively), but it did not alter the contractile responses induced by exogenous ACh. Pretreatment with the muscarinic M(2)-receptor agonist pilocarpine reduced the EFS-induced ACh release in the control tissues (p < 0.05), but not in the tissues incubated with IgE. The M(2)-receptor antagonist methoctramine significantly enhanced the EFS-induced contraction in control bronchi (p < 0.05), but this augmentation was not observed in the tissues incubated with IgE. These results suggest that IgE itself can enhance cholinergic bronchial contraction via facilitation of ACh release from cholinergic nerves and that this augmentation is related to autoreceptor M(2) dysfunction at nerve endings.