Smoke inhalation injury is the leading cause of death in firefighters and victims. Inhaled hot air and toxic smoke are the predominant hazards to the respiratory epithelium. We aimed to analyze the effects of thermal stress and smoke aldehyde on the permeability of the airway epithelial barrier. Transepithelial resistance (RTE) and short-circuit current (ISC) of mouse tracheal epithelial monolayers were digitized by an Ussing chamber setup. Zonula occludens-1 tight junctions were visualized under confocal microscopy. A cell viability test and fluorescein isothiocyanate-dextran assay were performed. Thermal stress (40°C) decreased RTE in a two-phase manner. Meanwhile, thermal stress increased ISC followed by its decline. Na+ depletion, amiloride (an inhibitor for epithelial Na+ channels [ENaCs]), ouabain (a blocker for Na+/K+-ATPase) and CFTRinh-172 (a blocker of cystic fibrosis transmembrane regulator [CFTR]) altered the responses of RTE and ISC to thermal stress. Steady-state 40°C increased activity of ENaCs, Na+/K+-ATPase, and CFTR. Acrolein, one of the main oxidative unsaturated aldehydes in fire smoke, eliminated RTE and ISC. Na+ depletion, amiloride, ouabain, and CFTRinh-172 suppressed acrolein-sensitive ISC, but showed activating effects on acrolein-sensitive RTE. Thermal stress or acrolein disrupted zonula occludens-1 tight junctions, increased fluorescein isothiocyanate-dextran permeability but did not cause cell death or detachment. The synergistic effects of thermal stress and acrolein exacerbated the damage to monolayers. In conclusion, the paracellular pathway mediated by the tight junctions and the transcellular pathway mediated by active and passive ion transport pathways contribute to impairment of the airway epithelial barrier caused by thermal stress and acrolein.

中文翻译：

---

烟气吸入损伤气道上皮屏障的离子传输机制

烟雾吸入伤害是消防员和受害者死亡的主要原因。吸入热空气和有毒烟雾是呼吸道上皮的主要危害。我们旨在分析热应激和烟醛对气道上皮屏障通透性的影响。小鼠气管上皮单层的上皮电阻（RTE）和短路电流（ISC）通过Ussing室设置数字化。在共聚焦显微镜下可视化Zonula occludens-1紧密连接。进行细胞活力测试和异硫氰酸荧光素-葡聚糖测定。热应力（40°C）以两相方式降低了RTE。同时，热应力增加，ISC随之下降。Na +耗竭，阿米洛利（阿米洛利（上皮Na +通道[ENaCs]抑制剂）），哇巴因（Na + / K + -ATPase的阻滞剂）和CFTRinh-172（囊性纤维化跨膜调节剂[CFTR]的阻滞剂）改变了RTE和ISC对热应激的反应。稳态40°C可增加ENaCs，Na + / K + -ATPase和CFTR的活性。丙烯醛是火烟中的主要氧化性不饱和醛之一，它消除了RTE和ISC。Na +耗竭，阿米洛利，哇巴因和CFTRinh-172抑制了对丙烯醛敏感的ISC，但对丙烯醛敏感RTE表现出活化作用。热应激或丙烯醛破坏了小带闭塞-1紧密连接，增加了异硫氰酸荧光素-葡聚糖的荧光素通透性，但没有引起细胞死亡或脱落。热应力和丙烯醛的协同作用加剧了对单层的损害。结论，