PT -期刊文章AU - Bonvini, Sara J. AU - Birrell, Mark A. AU - Dubuis, Eric AU - Adcock, John J. AU - Wortley, Michael A. AU - Flajolet, Pauline AU - Bradding, Peter AU - Belvisi，Maria G. TI -新型气道平滑肌-肥大细胞相互作用和TRPV4-ATP轴在非特应性哮喘中的作用AID - 10.1183/13993003.01458-2019 DP - 2020 01年7月TA -欧洲呼吸杂志PG - 1901458 VI - 56 IP - 1 4099 - //www.qdcxjkg.com/content/56/1/1901458.short 4100 - //www.qdcxjkg.com/content/56/1/1901458.full SO - Eur Respir J2020 01年7月;56 AB -肥大细胞-气道平滑肌(ASM)相互作用在哮喘患者免疫球蛋白(Ig)E依赖性支气管收缩中起主要作用，但对不依赖于ige的肥大细胞激活机制知之甚少。瞬时受体电位阳离子通道，亚家族V，成员4 (TRPV4)激活通过释放半胱氨酸白三烯(cyslt)引起人ASM收缩，但其机制尚不清楚。本研究的目的是探讨ige独立的肥大细胞- asm相互作用在trpv4诱导的支气管痉挛中的作用。在麻醉豚鼠中测量支气管收缩，并使用等距张力测量评估人和豚鼠气道组织的收缩。使用Ca2+敏感染料FURA2成像细胞内[Ca2+]的增加，并使用延时照相作为ASM细胞收缩的替代品。TRPV4拮抗剂GSK1016790A在豚鼠体内引起收缩，在人和豚鼠气管组织中，收缩被TRPV4拮抗剂GSK2193874抑制。GSK1016790A在人ASM细胞中增加[Ca2+]i并释放ATP而不引起收缩。TRPV4和ATP诱导离体气管组织收缩，但共培养实验表明需要人肺肥大细胞。 Expression profiling and pharmacological studies demonstrated that mast cell activation was dependent upon ATP activating the P2X4 receptor. Trypsin was shown to evoke contraction of tracheal tissue via activation of PAR-2-TRPV4-ATP-cysLT axis indicating the potential disease relevance of this signalling pathway.TRPV4 activation increases [Ca2+]i and releases ATP from ASM cells triggering P2X4-dependent release of cysLTs from mast cells resulting in ASM contraction. This study delineates a novel mast cell–ASM interaction and TRPV4 as a driver of IgE-independent mast cell-dependent bronchospasm.A technique not previously applied to respiratory research now uncovers important IgE-independent mechanisms involved in human mast cell–airway smooth muscle interactions that may be responsible for the bronchospasm associated with non-atopic asthma http://bit.ly/2U1n5nT