% 0期刊文章%莎拉J . Bonvini % Eric Dubuis马克·A·博雷尔% %约翰·J·爱德考克%迈克尔·A·沃尔特利% Pauline Flajolet %彼得·布拉德%玛丽亚·g·Belvisi % T小说气道平滑muscle-mast细胞相互作用和角色TRPV4-ATP轴non-atopic哮喘% D J 2020% R 10.1183/13993003.01458 -2019%欧洲呼吸杂志% P 1901458 % X原理桅杆cell-airway平滑肌(ASM)相互作用中发挥重要作用的IgE——依赖在哮喘支气管收缩看到但IgE-independent肥大细胞活化机制所知甚少。TRPV4激活引起收缩的人类ASM通过半胱氨酰白三烯等的释放(cysLTs),但机制尚不清楚。目的探讨IgE-independent角色,桅杆cell-ASM互动TRPV4-induced支气管痉挛。方法以犀牛因为豚鼠支气管收缩和收缩的人类和豚鼠气道组织评估使用等距张力测量。增加细胞内[Ca2 +]我是使用Ca2 +敏感染料FURA2成像,和延时ptychography是利用代理ASM细胞的收缩。结果TRPV4兴奋剂GSK1016790A收缩引起的豚鼠体内,并在人类和豚鼠气管组织,这是由TRPV4拮抗剂GSK2193874抑制。GSK1016790A增加[Ca2 +]我在人类ASM细胞释放ATP不会引起收缩。TRPV4和ATP引起收缩在孤立的气管组织培养实验表明要求人类肺肥大细胞。表达分析和药理研究表明,肥大细胞激活是依赖ATP激活P2X4受体。胰蛋白酶是显示唤起收缩气管组织通过激活PAR-2-TRPV4-ATP-cystLT轴指示信号通路的潜在疾病的相关性。结论TRPV4激活增加[Ca2 +]我和从ASM细胞释放ATP触发P2X4-dependent从肥大细胞释放cysLTs导致ASM收缩。这个研究描绘了桅杆cell-ASM交互和TRPV4 IgE-independent桅杆的司机cell-dependent支气管痉挛。FootnotesThis手稿最近发表在《欧洲呼吸杂志》上。 It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Bonvini has nothing to disclose.Conflict of interest: Dr. Birrell has nothing to disclose.Conflict of interest: Dr. DUBUIS has nothing to disclose.Conflict of interest: Dr. Adcock has nothing to disclose.Conflict of interest: Dr. Wortley has nothing to disclose.Conflict of interest: Dr. Flajolet has nothing to disclose.Conflict of interest: Dr. Bradding has nothing to disclose.Conflict of interest: Dr. Belvisi reports grants from Wellcome Trust, grants from Medical Research Council, from null, during the conduct of the study; personal fees and other from AstraZeneca, from null, outside the submitted work. %U //www.qdcxjkg.com/content/erj/early/2020/03/12/13993003.01458-2019.full.pdf