E-Cigarette Use Causes a Unique Innate Immune Response in the Lung, Involving Increased Neutrophilic Activation and Altered Mucin Secretion
E-Cigarette Use Causes a Unique Innate Immune Response in the Lung, Involving Increased Neutrophilic Activation and Altered Mucin Secretion
复制标题
使用电子烟会在肺部引发一种独特的先天免疫反应，包括中性粒细胞活化增加以及黏蛋白分泌改变。
DOI：
10.1164/rccm.201708-1590oc
复制
发表时间：
2018-02-15
影响因子：
24.7
通讯作者：
Kesimer, Mehmet
中科院分区：
文献类型：
--
作者：
Reidel, Boris;Radicioni, Giorgia;Kesimer, Mehmet
基本原理：电子烟越来越受欢迎，但人们对其潜在的不良健康影响知之甚少。目的：确定电子烟使用对气道的影响。方法：通过定量蛋白质组学分析了来自吸烟者、电子烟使用者和非吸烟者的诱导痰样本，并通过光散射/折射法和标记质谱法测定粘蛋白MUC 5AC和MUC 5 B的总浓度和个体浓度，分别中性粒细胞胞外陷阱（NET）的形成率也确定为相同groups.Measurements和主要结果：电子烟用户表现出显着增加与香烟烟雾相关的去乙酰化解毒和氧化应激相关的蛋白质与非吸烟者相比。与慢性阻塞性肺疾病相关的先天防御蛋白，如弹性蛋白酶和基质金属蛋白酶-9的水平在电子烟使用者中也显著升高。电子烟使用者的痰液还独特地表现出中性粒细胞相关和NET相关蛋白质的显著增加，例如髓过氧化物酶、天青杀素和蛋白质精氨酸脱亚胺酶4，尽管中性粒细胞计数没有显著升高。来自电子烟使用者的外周中性粒细胞显示出对佛波醇12-肉豆蔻酸酯13-乙酸酯诱导的NETosis的易感性增加。最后，气道粘液的凝胶形成构件的组成变化（即，结论：总之，我们的研究结果表明，电子烟的使用改变了气道分泌物中先天防御蛋白的分布，诱导了相对于吸烟的类似和独特的变化。这些数据挑战了电子烟是香烟更健康替代品的概念。
Rationale: E-cigarettes have become increasingly popular and little is known about their potential adverse health effects.Objectives: To determine the effects of e-cigarette use on the airways.Methods: Induced sputum samples from cigarette smokers, e-cigarette users, and nonsmokers were analyzed by quantitative proteomics, and the total and individual concentrations of mucins MUC5AC and MUC5B were determined by light scattering/refractometry and labeled mass spectrometry, respectively. Neutrophil extracellular trap (NET) formation rates were also determined for the same groups.Measurements and Main Results: E-cigarette users exhibited significant increases in aldehyde-detoxification and oxidative stress-related proteins associated with cigarette smoke compared with nonsmokers. The levels of innate defense proteins associated with chronic obstructive pulmonary disease, such as elastase and matrix metalloproteinase-9, were significantly elevated in e-cigarette users as well. E-cigarette users' sputum also uniquely exhibited significant increases in neutrophil granulocyte-related and NET-related proteins, such as myeloperoxidase, azurocidin, and protein-arginine deiminase 4, despite no significant elevation in neutrophil cell counts. Peripheral neutrophils from e-cigarette users showed increased susceptibility to phorbol 12-myristate 13-acetate-induced NETosis. Finally, a compositional change in the gel-forming building blocks of airway mucus (i.e., an elevated concentration of mucin MUC5AC) was observed in both cigarette smokers and e-cigarette users.Conclusions: Together, our results indicate that e-cigarette use alters the profile of innate defense proteins in airway secretions, inducing similar and unique changes relative to cigarette smoking. These data challenge the concept that e-cigarettes are a healthier alternative to cigarettes.