Secondhand smoke inhibits both Cl- and K+ conductances in normal human bronchial epithelial cells

Amy N Savitski,Ian A Blair,James L Kreindler,Noam A Cohen,Clementina Mesaros

doi:10.1186/1465-9921-10-120

Abstract

Secondhand smoke (SHS) exposure is an independent risk factor for asthma, rhinosinusitis, and more severe respiratory tract infections in children and adults. Impaired mucociliary clearance with subsequent mucus retention contributes to the pathophysiology of each of these diseases, suggesting that altered epithelial salt and water transport may play an etiological role. To test the hypothesis that SHS would alter epithelial ion transport, we designed a system for in vitro exposure of mature, well-differentiated human bronchial epithelial cells to SHS. We show that SHS exposure inhibits cAMP-stimulated, bumetanide-sensitive anion secretion by 25 to 40% in a time-dependent fashion in these cells. Increasing the amount of carbon monoxide to 100 ppm from 5 ppm did not increase the amount of inhibition, and filtering SHS reduced inhibition significantly. It was determined that SHS inhibited cAMP-dependent apical membrane chloride conductance by 25% and Ba2+-sensitive basolateral membrane potassium conductance by 50%. These data confirm previous findings that cigarette smoke inhibits chloride secretion in a novel model of smoke exposure designed to mimic SHS exposure. They also extend previous findings to demonstrate an effect on basolateral K+ conductance. Therefore, pharmacological agents that increase either apical membrane chloride conductance or basolateral membrane potassium conductance might be of therapeutic benefit in patients with diseases related to SHS exposure.

Highlights

Tobacco use is a worldwide epidemic accounting for 3% of the world's morbidity and mortality at a cost of tens of billions of U.S dollars annually [1]
By clamping the inlet and outlet tracts of the exposure chamber, carbon monoxide (CO) concentration could be held within a narrow range (5 - 10 ppm) (Fig. 1D), there was a slow drift of CO
To demonstrate deposition of a known constituent of cigarette smoke onto cells in the chamber, we placed 200 μl of warm PBS on the apical surface of human bronchial epithelial cells (HBECs) exposed to secondhand smoke (SHS) for 30 min and measured nicotine in the collected mucosal surface washes by mass spectrometry

Summary

Introduction

Tobacco use is a worldwide epidemic accounting for 3% of the world's morbidity and mortality at a cost of tens of billions of U.S dollars annually [1]. A recent study released by the Social Climate Survey of Tobacco from the Mississippi State University http://socialcli mate.org/ suggested that more than 40% of American children are exposed to secondhand smoke (SHS). This exposure is a significant risk factor for respiratory diseases, including lower airways infections, chronic rhinosinusitis,. Respiratory Research 2009, 10:120 http://respiratory-research.com/content/10/1/120 middle ear infection, and asthma in adults [3], as well as asthma and more severe respiratory syncytial virus (RSV) infection in children [4,5] These diseases, while clearly multifactorial, all share a component of impaired mucociliary clearance (MCC) and mucus retention

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Results

Conclusion