Short-term exposure of female BALB/cJ mice to e-cigarette aerosol promotes neutrophil recruitment and enhances neutrophil-platelet aggregation in pulmonary microvasculature

Despite the perception that e-cigarettes are safer than conventional cigarettes, numerous findings demonstrated that e-cigarette aerosol (EC) exposure induced compromised immune functionality, vascular changes even after acute exposure, and lung injury. Notably, altered neutrophil functionality and platelet hemodynamics have been observed post-EC exposure. It was hypothesized that EC exposure initiates an inflammatory response resulting in altered neutrophil behavior and increased neutrophil-platelet interaction in the pulmonary microvasculature. Neutrophil and platelet responses were examined up to 48 hrs following whole-body, short-term EC exposure without flavorants or nicotine in a murine model, which most closely modeled secondhand exposure. This study is the first to investigate the impact of EC exposure through lung intravital imaging. Compared to room air-exposed mice, EC-exposed mice displayed significantly increased 1.7‒1.9-fold number of neutrophils in the pulmonary microvasculature associated with no marked change in neutrophils within whole blood or bronchoalveolar lavage fluid (BALF). Neutrophil-platelet interactions were also significantly elevated 1.9‒2.5-fold in exposed mice. Plasma concentration of myeloperoxidase was markedly reduced 1.5-fold 48 hr following exposure cessation, suggesting suppressed neutrophil antimicrobial activity. Cytokine expression exhibited changes indicating vascular damage. Effects persisted for 48 hr post-EC exposure. Data demonstrated that EC exposure repeated for 3 consecutive days in 2.5 hr intervals in the absence of flavorants or nicotine resulted in modified pulmonary vasculature hemodynamics, altered immune functionality, and a pro-inflammatory state in female BALB/cJ mice.尽管大众普遍认为电子烟相较于传统卷烟更为安全，但已有大量研究结果证实，电子烟气溶胶（e-cigarette aerosol, EC）暴露可导致免疫功能受损、血管结构改变（即便在急性暴露后）以及肺损伤。值得注意的是，在电子烟气溶胶暴露后，已观察到中性粒细胞功能与血小板血流动力学发生改变。有研究提出假说：电子烟气溶胶暴露会触发炎症反应，进而导致肺微血管内中性粒细胞行为异常以及中性粒细胞-血小板相互作用增强。本研究在与二手烟暴露场景最为贴近的小鼠模型中，对不含调味剂与尼古丁的短期全身电子烟气溶胶暴露后48小时内的中性粒细胞与血小板反应进行了检测。本研究为首项通过肺活体成像技术探究电子烟气溶胶暴露影响的相关研究。与暴露于洁净空气的小鼠相比，电子烟气溶胶暴露小鼠的肺微血管内中性粒细胞数量显著升高1.7~1.9倍，而其全血或支气管肺泡灌洗液（bronchoalveolar lavage fluid, BALF）中的中性粒细胞数量并无明显变化。暴露小鼠体内的中性粒细胞-血小板相互作用也显著增强1.9~2.5倍。暴露结束48小时后，小鼠血浆中的髓过氧化物酶浓度显著降低1.5倍，这提示中性粒细胞的抗菌活性受到抑制。细胞因子的表达变化也提示存在血管损伤。上述效应在电子烟气溶胶暴露后可持续48小时。研究数据显示，在不含调味剂与尼古丁的条件下，以每2.5小时一次的频率连续3天暴露于电子烟气溶胶，会导致雌性BALB/cJ小鼠的肺微血管血流动力学改变、免疫功能受损，并出现促炎状态。