Division of Pulmonary Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Respir Res. 2009 Nov 27;10(1):120. doi: 10.1186/1465-9921-10-120.
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.
二手烟(SHS)暴露是儿童和成人哮喘、鼻旁窦炎和更严重呼吸道感染的独立危险因素。黏膜纤毛清除功能受损导致黏液潴留,这有助于解释这些疾病的病理生理学,表明上皮细胞盐和水转运的改变可能发挥着病因学作用。为了验证 SHS 会改变上皮细胞离子转运的假说,我们设计了一个体外暴露成熟、分化良好的人支气管上皮细胞于 SHS 的系统。我们发现 SHS 暴露以时间依赖性方式抑制了细胞内 cAMP 刺激的、布美他尼敏感的阴离子分泌 25%至 40%。将一氧化碳的量从 5 ppm 增加到 100 ppm 并没有增加抑制程度,而过滤 SHS 则显著减少了抑制作用。结果表明,SHS 抑制了 cAMP 依赖性顶端膜氯离子电导 25%,并抑制了 Ba2+敏感的基底外侧膜钾电导 50%。这些数据证实了先前的发现,即香烟烟雾在设计用于模拟 SHS 暴露的新型烟雾暴露模型中抑制了氯离子分泌。它们还扩展了先前的发现,证明了对基底外侧 K+电导的影响。因此,增加顶端膜氯离子电导或基底外侧膜钾电导的药物可能对与 SHS 暴露相关的疾病患者具有治疗益处。