Airway epithelial anion secretion and barrier function following exposure to fungal aeroallergens: role of oxidative stress.

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American journal of physiology. Cell physiology, ISSN: 1522-1563, Vol: 313, Issue: 1, Page: C68-C79

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Zaidman, Nathan A; O'Grady, Kelly E; Patil, Nandadevi; Milavetz, Francesca; Maniak, Peter J; Kita, Hirohito; O'Grady, Scott M
American Physiological Society
Biochemistry, Genetics and Molecular Biology
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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.