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

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Aeroaller-gens produced by Alternaria alternata can elicit life-threatening exacerbations of asthma in patients sensitized to this fungus. In this study, the effect of Alternaria on ion transport mechanisms underlying mucociliary clearance and airway epithelial barrier function was investigated in human airway epithelial cells. 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 effect was dependent on the increase in ROS. However, the Alternaria-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 Alternaria was responsible for regulating Ca2+-dependent anion secretion and tight junction electrical resistance that would be expected to affect mucociliary clearance.

Original languageEnglish (US)
Pages (from-to)C68-C79
JournalAmerican Journal of Physiology - Cell Physiology
Volume313
Issue number1
DOIs
StatePublished - Jan 1 2017

Fingerprint

Alternaria
Anions
Oxidative Stress
Mucociliary Clearance
Reactive Oxygen Species
Tight Junctions
NADPH Oxidase
Ion Transport
Electron Transport
Dextrans
Electric Impedance
Oxidants
Glutathione
Chlorides
Fungi
Asthma
Epithelium
Adenosine Triphosphate
Epithelial Cells

Keywords

  • ATP release
  • Chloride secretion
  • Intracellular calcium
  • Tight junctions

Cite this

Airway epithelial anion secretion and barrier function following exposure to fungal aeroallergens : Role of oxidative stress. / Zaidman, Nathan A.; O’Grady, Kelly E.; Patil, Nandadevi; Milavetz, Francesca; Maniak, Peter J.; Kita, Hirohito; O’Grady, Scott M.

In: American Journal of Physiology - Cell Physiology, Vol. 313, No. 1, 01.01.2017, p. C68-C79.

Research output: Contribution to journalArticle

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