Rasmussen Lawrence W, Finley Dakota C, Smith Julian B, Noa Aaron S, Blalock J Edwin, Gaggar Amit, Madison Matthew C
Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States.
Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL, United States.
Front Immunol. 2025 Aug 27;16:1665936. doi: 10.3389/fimmu.2025.1665936. eCollection 2025.
While e-cigarette use (vaping) has increased in the last decade, its effects on airway inflammation and extracellular vesicle (EV) biology remain unclear. This study examined how long-term and acute vapor exposures influence lung immune responses, neutrophilic inflammation, and EV-associated proteolytic activity.
Mice were exposed daily to vapor from commercial e-cigarettes or room air for up to 12 weeks. After exposure, we assessed immune cell recruitment, alveolar damage, and EV populations in the airways. To explore vapor-mediated effects on secondary lung injury, a lipopolysaccharide (LPS) challenge was administered after two weeks of vapor exposure. We then analyzed immune cell responses and isolated neutrophil-derived EVs (nEVs) for transfer into naïve mice to evaluate pathogenic potential.
Vapor exposure alone did not significantly alter immune cell infiltration, lung histology, or EV protease activity. However, mice pre-exposed to vapor and then challenged with LPS showed increased neutrophil infiltration, elevated neutrophil elastase activity in EVs, and greater alveolar damage. Furthermore, nEVs from these mice induced more severe emphysematous changes when transferred to unexposed mice.
While e-cigarette vapor alone does not provoke marked airway inflammation or proteolytic EV release, it creates a primed immune state. This priming amplifies inflammatory and destructive responses to subsequent challenges. These findings suggest vaping may exacerbate lung damage when combined with infections or other environmental stressors, raising concerns about its role in worsening pulmonary disease.
在过去十年中，电子烟的使用（吸电子烟）有所增加，但其对气道炎症和细胞外囊泡（EV）生物学的影响仍不清楚。本研究考察了长期和急性吸入电子烟蒸汽如何影响肺部免疫反应、中性粒细胞炎症以及与EV相关的蛋白水解活性。
将小鼠每天暴露于市售电子烟产生的蒸汽或室内空气中，长达12周。暴露后，我们评估了气道中的免疫细胞募集、肺泡损伤和EV群体。为了探究蒸汽对继发性肺损伤的影响，在蒸汽暴露两周后给予脂多糖（LPS）刺激。然后我们分析了免疫细胞反应，并分离出中性粒细胞衍生的EV（nEV），将其转移到未接触过的小鼠体内，以评估其致病潜力。
单独的蒸汽暴露并未显著改变免疫细胞浸润、肺组织学或EV蛋白酶活性。然而，预先暴露于蒸汽然后接受LPS刺激的小鼠显示出中性粒细胞浸润增加、EV中中性粒细胞弹性蛋白酶活性升高以及更严重的肺泡损伤。此外，将这些小鼠的nEV转移到未暴露的小鼠体内时，会诱发更严重的肺气肿变化。
虽然单独的电子烟蒸汽不会引发明显的气道炎症或蛋白水解性EV释放，但它会产生一种致敏的免疫状态。这种致敏会放大对后续刺激的炎症和破坏性反应。这些发现表明，吸电子烟与感染或其他环境应激源结合时可能会加剧肺损伤，这引发了人们对其在加重肺部疾病中作用的担忧。
