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Sci Rep . Cigarette smoke increases susceptibility of alveolar macrophages to SARS-CoV-2 infection through inducing reactive oxygen species-upregul

tetano

Editor, Senior Moderator
Sci Rep


. 2023 May 16;13(1):7894.
doi: 10.1038/s41598-023-34785-6. Cigarette smoke increases susceptibility of alveolar macrophages to SARS-CoV-2 infection through inducing reactive oxygen species-upregulated angiotensin-converting enzyme 2 expression

Chin-Wei Kuo[SUP] 1 2 [/SUP], Po-Lan Su[SUP] 2 [/SUP], Tang-Hsiu Huang[SUP] 1 2 [/SUP], Chien-Chung Lin[SUP] 2 [/SUP], Chian-Wei Chen[SUP] 2 [/SUP], Jeng-Shiuan Tsai[SUP] 2 [/SUP], Xin-Min Liao[SUP] 1 2 [/SUP], Tzu-Yi Chan[SUP] 2 [/SUP], Chi-Chang Shieh[SUP] 3 4 [/SUP]



Affiliations
Abstract

Alveolar macrophages (AMs) are the drivers of pulmonary cytokine storm in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This study aimed to investigate clinical-regulatory factors for the entrance protein of SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2) in AMs. Human AMs were collected from 56 patients using bronchoalveolar lavage. ACE2 expression in AMs was positively correlated with smoking pack-year (Spearman's r = 0.347, P = 0.038). In multivariate analysis, current smoking was associated with increased ACE2 in AMs (β-coefficient: 0.791, 95% CI 0.019-1.562, P = 0.045). In vitro study, ex-vivo human AMs with higher ACE2 were more susceptible to SARS-CoV-2 pseudovirus (CoV-2 PsV). Treating human AMs using cigarette smoking extract (CSE) increases the ACE2 and susceptibility to CoV-2 PsV. CSE did not significantly increase the ACE2 in AMs of reactive oxygen species (ROS) deficient Cybb[SUP]-/-[/SUP] mice; however, exogenous ROS increased the ACE2 in Cybb[SUP]-/-[/SUP] AMs. N-acetylcysteine (NAC) decreases ACE2 by suppressing intracellular ROS in human AMs. In conclusion, cigarette smoking increases the susceptibility to SARS-CoV-2 by increasing ROS-induced ACE2 expression of AMs. Further investigation into the preventive effect of NAC on the pulmonary complications of COVID-19 is required.


 
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