Electronic nicotine delivery system (ENDS) use is outpacing our understanding of its potential harmful effects. Homeostasis of the lung is maintained through proper balance of cell death, efferocytic clearance, and phagocytosis of pathogens. To investigate whether ENDS use has the potential to alter this balance, we developed physiologically relevant ENDS exposure paradigms for lung epithelial cells and primary macrophages. In our studies, cells were exposed directly to aerosol made from carefully controlled components with and without nicotine. We found that ENDS aerosol exposure led to apoptosis, secondary necrosis, and necrosis in lung epithelial cell models. In contrast, macrophages died mostly by apoptosis and inflammatory caspase–mediated cell death when exposed to ENDS aerosol. The clearance of dead cells and pathogens by efferocytosis and phagocytosis, respectively, is an important process in maintaining a healthy lung. To investigate the impact of ENDS aerosol on macrophage function independent of general toxicity, we used an exposure time that did not induce cell death in primary macrophages. Exposure to ENDS aerosol containing nicotine inhibited nearly all phagocytic and greatly reduced the efferocytic abilities of primary macrophages. When challenged with a bacterial pathogen, there was decreased bacterial clearance. The presence of nicotine in the ENDS aerosol increased its toxicity and functional impact; however, nicotine exposure alone did not have any deleterious effects. These data demonstrate that ENDS aerosol exposure could lead to increased epithelial cell and macrophage death in the lung and impair important macrophage functions that are essential for maintenance of lung function.

电子尼古丁传送系统 (ENDS) 的使用超出了我们对其潜在有害影响的理解。肺的稳态是通过细胞死亡、细胞清除和病原体吞噬的适当平衡来维持的。为了研究 ENDS 的使用是否有可能改变这种平衡，我们为肺上皮细胞和原代巨噬细胞开发了生理相关的 ENDS 暴露范式。在我们的研究中，细胞直接暴露于气溶胶​​中，气溶胶由含有和不含尼古丁的精心控制的成分制成。我们发现 ENDS 气溶胶暴露导致肺上皮细胞模型中的细胞凋亡、继发性坏死和坏死。相比之下，当暴露于 ENDS 气溶胶时，巨噬细胞主要死于细胞凋亡和炎症性半胱天冬酶介导的细胞死亡。分别通过胞吞作用和吞噬作用清除死细胞和病原体是维持健康肺的重要过程。为了研究 ENDS 气溶胶对巨噬细胞功能的影响，与一般毒性无关，我们使用了不会诱导原代巨噬细胞细胞死亡的暴露时间。暴露于含有尼古丁的 ENDS 气雾剂几乎抑制了所有吞噬细胞，并大大降低了原代巨噬细胞的吞噬能力。当受到细菌病原体的攻击时，细菌清除率降低。ENDS 气雾剂中尼古丁的存在增加了其毒性和功能影响；然而，单独接触尼古丁并没有任何有害影响。