Chronic E-Cigarette Use Increases Neutrophil Elastase and Matrix Metalloprotease Levels in the Lung
Chronic E-Cigarette Use Increases Neutrophil Elastase and Matrix Metalloprotease Levels in the Lung
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DOI：
10.1164/rccm.201903-0615oc
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发表时间：
2019-12-01
影响因子：
24.7
通讯作者：
Tarran, Robert
中科院分区：
文献类型：
--
作者：
Ghosh, Arunava;Coakley, Raymond D.;Tarran, Robert
原理：蛋白水解是肺先天免疫系统的一个关键方面。蛋白酶，包括中性粒细胞弹性蛋白酶和MMP（基质金属蛋白酶），通过切割其靶蛋白来调节细胞信号传导、炎症、组织重塑和白细胞募集。过度的蛋白质水解发生在长期使用烟草的情况下，是支气管扩张和肺气肿的病因。电子烟（vaping）对蛋白水解的影响尚不清楚。Objectives：我们使用蛋白酶水平作为伤害的生物标志物，以确定vaping对lung.Methods的影响：我们对健康的非吸烟者，吸烟者和电子烟使用者（vapers）进行了研究性支气管镜检查，并确定了BAL中的蛋白酶水平。同时，我们研究了电子烟组分对分离的人血液中性粒细胞和BAL-derived巨噬细胞中蛋白酶分泌的影响。我们还分析了诱导痰和BAL.Measurements和主要结果中的尼古丁浓度：神经弹性蛋白酶，MMP-2和MMP-9的活性和蛋白质水平同样升高，在这两个vapers和吸烟者的BAL相对于非吸烟者。相反，抗蛋白酶水平不变。我们还发现，暴露于尼古丁的孤立的中性粒细胞和巨噬细胞引起蛋白酶释放的剂量依赖性增加。吸电子烟后，可测量的尼古丁水平检测痰液和BAL，这对应于在免疫cells.Conclusions中看到的蛋白酶释放的半最大有效浓度值：我们得出结论，吸电子烟诱导尼古丁依赖性蛋白酶释放从居民肺免疫细胞。因此，长期吸烟通过增加肺部的蛋白水解破坏了蛋白酶-抗蛋白酶平衡，这可能使吸烟者面临患慢性肺部疾病的风险。这些数据表明，电子烟可能并不比吸烟更安全。
Rationale: Proteolysis is a key aspect of the lung's innate immune system. Proteases, including neutrophil elastase and MMPs (matrix metalloproteases), modulate cell signaling, inflammation, tissue remodeling, and leukocyte recruitment via cleavage of their target proteins. Excessive proteolysis occurs with chronic tobacco use and is causative for bronchiectasis and emphysema. The effect of e-cigarettes (vaping) on proteolysis is unknown.Objectives: We used protease levels as biomarkers of harm to determine the impact of vaping on the lung.Methods: We performed research bronchoscopies on healthy nonsmokers, cigarette smokers, and e-cigarette users (vapers), and determined protease levels in BAL. In parallel, we studied the effects of e-cigarette components on protease secretion in isolated human blood neutrophils and BAL-derived macrophages. We also analyzed the nicotine concentration in induced sputum and BAL.Measurements and Main Results: Neutrophil elastase, MMP-2, and MMP-9 activities and protein levels were equally elevated in both vapers' and smokers' BAL relative to nonsmokers. In contrast, antiprotease levels were unchanged. We also found that exposure of isolated neutrophils and macrophages to nicotine elicited dose-dependent increases in protease release. After vaping, measurable levels of nicotine were detectable in sputum and BAL, which corresponded to the half-maximal effective concentration values for protease release seen in immune cells.Conclusions: We conclude that vaping induces nicotine-dependent protease release from resident pulmonary immune cells. Thus, chronic vaping disrupts the protease-antiprotease balance by increasing proteolysis in lung, which may place vapers at risk of developing chronic lung disease. These data indicate that vaping may not be safer than tobacco smoking.