Zaidman Nathan A, O'Grady Kelly E, Patil Nandadevi, Milavetz Francesca, Maniak Peter J, Kita Hirohito, O'Grady Scott M
Department of Integrative Biology and Physiology University of Minnesota, Minneapolis, Minnesota.
Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, Minnesota; and.
Am J Physiol Cell Physiol. 2017 Jul 1;313(1):C68-C79. doi: 10.1152/ajpcell.00043.2017. Epub 2017 Apr 26.
Aeroallergens produced by can elicit life-threatening exacerbations of asthma in patients sensitized to this fungus. In this study, the effect of on ion transport mechanisms underlying mucociliary clearance and airway epithelial barrier function was investigated in human airway epithelial cells. Apical exposure to induced an increase in anion secretion that was inhibited by blockers of CFTR and Ca-activated Cl channels. Stimulation of anion secretion was dependent on Ca uptake from the apical solution. exposure also produced an increase in reactive oxygen species (ROS) that was blocked by pretreatment with the oxidant scavenger glutathione (GSH). GSH and the NADPH oxidase inhibitor/complex 1 electron transport inhibitor diphenylene iodonium chloride (DPI) blocked ATP release and the increase in intracellular [Ca] evoked by also decreased transepithelial resistance, and a portion of this effect was dependent on the increase in ROS. However, the -induced increase in unidirectional dextran (molecular mass = 4,000 Da) flux across the epithelium could not be accounted for by increased oxidative stress. These results support the conclusion that oxidative stress induced by was responsible for regulating Ca-dependent anion secretion and tight junction electrical resistance that would be expected to affect mucociliary clearance.
由……产生的气传变应原可在对这种真菌敏感的患者中引发危及生命的哮喘加重。在本研究中，在人气道上皮细胞中研究了……对黏液纤毛清除和气道上皮屏障功能潜在的离子转运机制的影响。顶端暴露于……会诱导阴离子分泌增加，这被囊性纤维化跨膜传导调节因子（CFTR）和钙激活氯离子通道阻滞剂所抑制。阴离子分泌的刺激依赖于从顶端溶液中摄取钙。……暴露还会使活性氧（ROS）增加，这被用氧化剂清除剂谷胱甘肽（GSH）预处理所阻断。GSH和NADPH氧化酶抑制剂/复合物1电子传递抑制剂二苯基碘鎓氯化物（DPI）阻断ATP释放，并且……诱发的细胞内[Ca]增加也降低了跨上皮电阻，并且这种效应的一部分依赖于ROS的增加。然而，……诱导的单向葡聚糖（分子量 = 4000 Da）跨上皮通量增加不能用氧化应激增加来解释。这些结果支持这样的结论，即……诱导的氧化应激负责调节钙依赖性阴离子分泌和紧密连接电阻，这有望影响黏液纤毛清除。
