ty -jour t1-新型气道平滑肌 - 天然电池相互作用,以及在非原子哮喘JF中TRPV4 -ATP轴的作用 - 欧洲呼吸杂志JO -EUR RESSIR J DO -10.1183/13993003.014588-2019SP -1901458 AU -Bonvini,Sara J. Au -Birrell,Mark A. Au -Dubuis,Eric Au -Adcock,John J. Au -Wortley -Wortley,Michael A. Au -Flajolet -Flajolet,Pauline au -pauline au -Bradding,Peter Au -Belvisi,Belvisi,belvisi,belvisi,Maria G. Y1-2020/07/01 Ur -http://www.qdcxjkg.com/content/56/1/1/1/1901458.Abstract N2-桅杆细胞 - 摩尔道平面肌肉(ASM)相互作用在免疫球蛋白中起主要作用(IG)在哮喘中看到的电子依赖的支气管收缩,但对肥大细胞活化的IgE独立机制知之甚少。瞬态受体电势阳离子通道,亚家族V,成员4(TRPV4)激活通过释放白细胞三烯(CYSLTS)引起人ASM的收缩,但该机制未知。本研究的目的是研究在TRPV4诱导的支气管菌中IgE独立的,肥大细胞 - 溶质的相互作用的作用,并在麻醉的豚鼠中测量了人类和豚鼠气道的收缩,并使用等距张力测量进行了评估。使用Ca2+敏感的染料Fura2对细胞内[Ca2+]的增加增加,并将延时的Ptychography用作ASM细胞收缩的替代物。TRPV4激动剂GSK1016790A导致了几内亚猪的体内和几内亚猪的收缩,在豚鼠和豚鼠中引起了收缩。- 气管组织,由TRPV4拮抗剂GSK2193874抑制。GSK1016790A增加了[Ca2+] I,并在人ASM细胞中释放了ATP而不会引起收缩。TRPV4和ATP在分离的气管组织中诱发了收缩,但共培养实验表明对人肺肥大细胞的要求。表达分析和药理学研究表明,肥大细胞激活取决于ATP激活P2X4受体。 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 ER -