Ichinose M, Miura M, Tomaki M, Oyake T, Kageyama N, Ikarashi Y, Maruyama Y, Shirato K
First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Am J Respir Crit Care Med. 1996 Nov;154(5):1272-6. doi: 10.1164/ajrccm.154.5.8912735.
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 examined 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 M2-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 M2-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 M2 dysfunction at nerve endings.
气道胆碱能高反应性在哮喘患者中经常可见。近期报道提示IgE可能参与高反应性，尽管确切机制仍不明确。在本研究中，我们检测了与IgE孵育是否会促进人类气道的胆碱能功能。从20例接受肺切除术的患者获取支气管。通过电场刺激（EFS）或外源性乙酰胆碱（ACh）诱导胆碱能收缩反应，并通过等长张力测量进行评估。还通过高效液相色谱法测量EFS诱导的胆碱能神经释放ACh。与用热灭活IgE（对照）孵育的支气管相比，与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），但未改变外源性ACh诱导的收缩反应。用毒蕈碱M2受体激动剂毛果芸香碱预处理可降低对照组织中EFS诱导的ACh释放（p < 0.05），但在与IgE孵育组织中未降低。M2受体拮抗剂美索曲明显著增强对照支气管中EFS诱导的收缩（p < 0.05），但在与IgE孵育组织中未观察到这种增强。这些结果表明，IgE本身可通过促进胆碱能神经释放ACh来增强胆碱能支气管收缩，且这种增强与神经末梢自身受体M2功能障碍有关。
