Department of Cell Biology & Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
Int J Mol Sci. 2023 Oct 19;24(20):15348. doi: 10.3390/ijms242015348.
Proteases such as neutrophil elastase cleave and activate the epithelial sodium channel (ENaC), causing airway dehydration. Our current study explores the impact of increased protease levels in vapers' airways on ENaC activity and airway dehydration. Human bronchial epithelial cultures (HBECs) were exposed to bronchoalveolar lavage fluid (BALF) from non-smokers, smokers and vapers. Airway surface liquid (ASL) height was measured by confocal microscopy as a marker of hydration. ENaC cleavage was measured by Western blotting. Human peripheral blood neutrophils were treated with a menthol-flavored e-liquid (Juul), and the resulting secretions were added to HBECs. BALF from smokers and vapers significantly and equally increased ENaC activity and decreased ASL height. The ASL height decrease was attenuated by protease inhibitors. Non-smokers' BALF had no effect on ENaC or ASL height. BALF from smokers and vapers, but not non-smokers, induced ENaC cleavage. E-liquid-treated neutrophil secretions cleaved ENaC and decreased ASL height. Our study demonstrated that elevated protease levels in vapers' airways have functional significance since they can activate ENaC, resulting in airway dehydration. Lung dehydration contributes to diseases like cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD) and asthma. Thus, our data predict that vaping, like smoking, will cause airway surface dehydration that likely leads to lung disease.
蛋白酶，如中性粒细胞弹性蛋白酶，可裂解并激活上皮钠离子通道（ENaC），导致气道脱水。我们目前的研究探讨了气道中蛋白酶水平升高对 ENaC 活性和气道脱水的影响。我们将人支气管上皮细胞（HBEC）暴露于非吸烟者、吸烟者和电子烟使用者的支气管肺泡灌洗液（BALF）中。通过共聚焦显微镜测量气道表面液体（ASL）高度，作为水合作用的标志物。通过 Western blot 测量 ENaC 裂解。用薄荷醇风味的电子烟液（Juul）处理人外周血中性粒细胞，并将产生的分泌物添加到 HBEC 中。吸烟者和电子烟使用者的 BALF 显著且同等地增加了 ENaC 活性并降低了 ASL 高度。蛋白酶抑制剂可减弱 ASL 高度降低。非吸烟者的 BALF 对 ENaC 或 ASL 高度没有影响。只有吸烟者和电子烟使用者的 BALF 诱导了 ENaC 裂解。电子烟液处理的中性粒细胞分泌物裂解 ENaC 并降低了 ASL 高度。我们的研究表明，电子烟使用者气道中升高的蛋白酶水平具有功能意义，因为它们可以激活 ENaC，导致气道脱水。肺脱水会导致囊性纤维化（CF）、慢性阻塞性肺疾病（COPD）和哮喘等疾病。因此，我们的数据预测，与吸烟一样，电子烟也会导致气道表面脱水，这可能导致肺部疾病。
