Abstract
Objective: Tobacco-smoke exposure inhibits transepithelial Cl-secretion—a major determinant of airway surface liquid hydration and mucociliary clearance (MCC). The objective of the current study was to evaluate the effects of acrolein exposure (a tobacco smoke toxin) on Cl-transport through the major apical anion channel CFTR in sinonasal epithelium.
Method: Primary murine nasal septal (MNSE, wild type, and transgenic CFTR-/-) and human sinonasal epithelial (HSNE) cultures were exposed to acrolein in Ussing chambers, and effects on Cl-secretion were investigated using pharmacologic manipulation. Cellular cAMP signaling and cytotoxicity were also investigated.
Results: Acrolein-stimulated Cl-secretion (ΔISC - change in short-circuit current in µA/cm2) at low concentrations (100 µM, 15.8 ± 2.2 vs 2.4 ± 0.8 (control); p-transport at 300 µM (13.3 ± 1.2 vs 19.9 ± 1.0; p-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, indicating direct effects on the CFTR.
Conclusion: Decreased MCC is a major contributing feature to chronic rhinosinusitis. The present study demonstrated that acrolein has complex but direct interactions with CFTR. Robust inhibition of Cl-transport at higher concentrations indicates the potential contribution of this toxin to decreased MCC in individuals with chronic tobacco smoke exposure.
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