Airway epithelial anion secretion and barrier function following exposure to fungal aeroallergens: role of oxidative stress.
Airway epithelial anion secretion and barrier function following exposure to fungal aeroallergens: role of oxidative stress.
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接触真菌空气过敏原后气道上皮阴离子分泌和屏障功能：氧化应激的作用。
DOI：
10.1152/ajpcell.00043.2017
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发表时间：
2017
期刊：
影响因子：
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通讯作者：
O'Grady,ScottM
中科院分区：
文献类型：
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作者：
Zaidman,NathanA;O'Grady,KellyE;Patil,Nandadevi;Milavetz,Francesca;Maniak,PeterJ;Kita,Hirohito;O'Grady,ScottM
由链格孢菌产生的吸入性过敏原可引起对该真菌敏感的患者哮喘的危及生命的恶化。在这项研究中，链格孢菌对离子转运机制的影响，黏膜纤毛清除和气道上皮屏障功能的人气道上皮细胞进行了调查。根尖暴露于链格孢菌可导致阴离子分泌增加，而CFTR和Ca 2+激活的Cl−通道阻断剂可抑制阴离子分泌。对阴离子分泌的刺激依赖于从根尖溶液中摄取Ca ~（2+）。链格孢菌暴露也产生了活性氧（ROS）的增加，这种增加可被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电子传递抑制剂氯化二苯撑碘鎓（DPI）可阻断链格孢引起的ATP释放和胞内[Ca ~（2+）]增加，链格孢也可降低跨上皮电阻，这种作用部分依赖于ROS的增加。然而，链格孢菌诱导的单向葡聚糖（分子量= 4,000 Da）穿过上皮的通量增加不能被氧化应激增加所解释。这些结果支持了以下结论，即氧化应激引起的链格孢负责调节Ca 2+依赖的阴离子分泌和紧密连接电阻，预计将影响粘膜纤毛清除。
Aeroallergens produced byAlternaria alternatacan elicit life-threatening exacerbations of asthma in patients sensitized to this fungus. In this study, the effect ofAlternariaon ion transport mechanisms underlying mucociliary clearance and airway epithelial barrier function was investigated in human airway epithelial cells. Apical exposure toAlternariainduced an increase in anion secretion that was inhibited by blockers of CFTR and Ca2+-activated Cl−channels. Stimulation of anion secretion was dependent on Ca2+uptake from the apical solution.Alternariaexposure 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 [Ca2+] evoked byAlternaria.Alternariaalso decreased transepithelial resistance, and a portion of this effect was dependent on the increase in ROS. However, theAlternaria-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 byAlternariawas responsible for regulating Ca2+-dependent anion secretion and tight junction electrical resistance that would be expected to affect mucociliary clearance.