Apr 26, 2017

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

Nathan A. Zaidman, Kelly E. O'Grady, Nandadevi Patil, Francesca Milavetz, Peter J Maniak, Hirohito Kita, Scott M. O'Grady
American Journal of Physiology - Cell Physiology
  • States that aeroallergens produced by Alternaria alternata can elicit life-threatening exacerbations of asthma in patients sensitized to this fungus
  • Investigates the effect of Alternaria on ion transport mechanisms underlying mucociliary clearance and airway epithelial barrier function in human airway epithelial cells
  • Finds that:
    • Apical exposure to Alternaria induced 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
    • Alternaria 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 [Ca2+] evoked by Alternaria
    • Alternaria also decreased transepithelial resistance and a portion of this affect was dependent on the increase in ROS
    • However, the Alternaria-induced increase in unidirectional dextran (mw = 4000 Da) flux across the epithelium could not be accounted for by increased oxidative stress
  • Results support the conclusion that oxidative stress induced by Alternaria was responsible for regulating Ca2+-dependent anion secretion and tight junction electrical resistance that would be expected to affect mucociliary clearance