路边颗粒物与对SARS-CoV-2感染的易感性
Curbside particulate matter and susceptibility to SARS-CoV-2 infection.
作者信息
Miyashita Lisa, Foley Gary, Semple Sean, Gibbons Joseph M, Pade Corinna, McKnight Áine, Grigg Jonathan
机构信息
Blizard Institute, Queen Mary University of London, London, United Kingdom.
Institute for Social Marketing, University of Stirling, Stirling, United Kingdom.
出版信息
J Allergy Clin Immunol Glob. 2023 Jul 8;2(4):100141. doi: 10.1016/j.jacig.2023.100141. eCollection 2023 Nov.
BACKGROUND
Biologic plausibility for the association between exposure to particulate matter (PM) less than 10 μm in aerodynamic diameter (PM) and coronavirus disease 2019 (COVID-19) morbidity in epidemiologic studies has not been determined. The upregulation of angiotensin-converting enzyme 2 (ACE2), the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) entry receptor on host cells, by PM is a putative mechanism.
OBJECTIVE
We sought to assess the effect of PM on SARS-CoV-2 infection of cells .
METHODS
PM from the curbside of London's Marylebone Road and from exhaust emissions was collected by cyclone. A549 cells, human primary nasal epithelial cells (HPNEpCs), SARS-CoV-2-susceptible Vero-E6 and Calu3 cells were cultured with PM. ACE2 expression (as determined by median fluorescent intensity) was assessed by flow cytometry, and ACE2 mRNA transcript level was assessed by PCR. The role of oxidative stress was determined by N-acetyl cysteine. The cytopathic effect of SARS-CoV-2 (percentage of infection enhancement) and expression of SARS-CoV-2 genes' open reading frame (ORF) 1ab, S protein, and N protein (focus-forming units/mL) were assessed in Vero-E6 cells. Data were analyzed by either the Mann-Whitney test or Kruskal-Wallis test with the Dunn multiple comparisons test.
RESULTS
Curbside PM at concentrations of 10 μg/mL or more increased ACE2 expression in A549 cells ( = .0021). Both diesel PM and curbside PM in a concentration of 10 μg/mL increased ACE2 expression in HPNEpCs ( = .0022 and = .0072, respectively). ACE2 expression simulated by curbside PM was attenuated by N-acetyl cysteine in HPNEpCs ( = .0464). Curbside PM increased ACE2 expression in Calu3 cells ( = .0256). In Vero-E6 cells, curbside PM increased ACE2 expression ( = .0079), ACE2 transcript level ( = .0079), SARS-CoV-2 cytopathic effect ( = .0002), and expression of the SARS-CoV-2 genes' ORF1ab, S protein, and N protein ( = .0079).
CONCLUSIONS
Curbside PM increases susceptibility to SARS-COV-2 infection .
背景
在流行病学研究中，空气动力学直径小于10μm的颗粒物（PM）暴露与2019冠状病毒病（COVID-19）发病率之间关联的生物学合理性尚未确定。PM上调宿主细胞上的严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）进入受体血管紧张素转换酶2（ACE2）是一种可能的机制。
目的
我们试图评估PM对细胞感染SARS-CoV-2的影响。
方法
通过旋风分离器收集伦敦马里波恩路路边和尾气排放中的PM。将A549细胞、人原代鼻上皮细胞（HPNEpC）及对SARS-CoV-2敏感的Vero-E6和Calu3细胞与PM一起培养。通过流式细胞术评估ACE2表达（以中位荧光强度确定），通过PCR评估ACE2 mRNA转录水平。通过N-乙酰半胱氨酸确定氧化应激的作用。在Vero-E6细胞中评估SARS-CoV-2的细胞病变效应（感染增强百分比）以及SARS-CoV-2基因开放阅读框（ORF）1ab、S蛋白和N蛋白的表达（集落形成单位/毫升）。数据采用Mann-Whitney检验或Kruskal-Wallis检验及Dunn多重比较检验进行分析。
结果
浓度为10μg/mL及以上的路边PM可增加A549细胞中ACE2的表达（P = 0.0021）。浓度为10μg/mL的柴油PM和路边PM均可增加HPNEpC中ACE2的表达（分别为P = 0.0022和P = 0.0072）。在HPNEpC中，N-乙酰半胱氨酸可减弱路边PM模拟的ACE2表达（P = 0.0464）。路边PM可增加Calu3细胞中ACE2的表达（P = 0.0256）。在Vero-E6细胞中，路边PM可增加ACE2表达（P = 0.0079）、ACE2转录水平（P = 0.0079）、SARS-CoV-2细胞病变效应（P = 0.0002）以及SARS-CoV-2基因ORF1ab、S蛋白和N蛋白的表达（P = 0.0079）。
结论
路边PM会增加对SARS-CoV-2感染的易感性。
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