• The Laryngoscope · Jun 2012

    Comparative Study

    Cystic fibrosis transmembrane conductance regulator modulation by the tobacco smoke toxin acrolein.

    • Nathan S Alexander, Angela Blount, Shaoyan Zhang, Daniel Skinner, Stephen B Hicks, Michael Chestnut, Frederick A Kebbel, Eric J Sorscher, and Bradford A Woodworth.
    • Department of Surgery/Division of Otolaryngology, Birmingham, Alabama, USA.
    • Laryngoscope. 2012 Jun 1;122(6):1193-7.

    Objectives/HypothesisEvidence indicates that decreased mucociliary clearance (MCC) is a major contributing feature to chronic rhinosinusitis. Tobacco-smoke exposure is thought to inhibit transepithelial Cl(-) secretion, a major determinant of airway surface liquid hydration and MCC. The objective of the current study was to evaluate the effects of acrolein exposure (a prominent tobacco smoke toxin) on vectorial Cl(-) transport through the major apical anion channel cystic fibrosis transmembrane conductance regulator (CFTR) in sinonasal epithelium.Study DesignIn vitro investigation.MethodsPrimary murine nasal septal epithelia (MNSE; wild-type and transgenic CFTR(-/-)) cultures were exposed to acrolein in Ussing chambers and the effects on Cl(-) secretion investigated using pharmacologic manipulation. Cellular cyclic adenosine monophosphate (cAMP) signaling and cytotoxicity were also investigated.ResultsAcrolein stimulated Cl(-) secretion (ΔI(SC) - change in short-circuit current in μA/cm(2)) at concentrations similar to smoker's airways (100 μM, 15.8 ± 2.2 vs. 2.4 ± 0.8 [control]; P < .0001), suppressed forskolin-stimulated C- transport at 300 μM (13.3 ± 1.2 vs. 19.9 ± 1.0; P < .01), and completely abolished all transport at 500 μM (-1.1 ± 1.6). Stimulated Cl(-) secretion was solely reliant upon the presence of CFTR (confirmed in transgenic CFTR(-/-) MNSE), but independent of cAMP signaling. Inhibition at higher concentrations was not secondary to cellular cytotoxicity.ConclusionsThe present study demonstrates that acrolein has complex but pronounced interaction with the major apical Cl(-) transport mechanism that uses CFTR. Further investigations are required to determine acrolein's impact as a tobacco smoke constituent on mucociliary transport.Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

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