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, Po Lan Su, Tang Hsiu Huang, Chien Chung Lin, Chian Wei Chen, Jeng Shiuan Tsai, Xin Min Liao, Tzu Yi Chan, Chi Chang Shieh

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

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–/– mice; however, exogenous ROS increased the ACE2 in Cybb–/– 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.

Original languageEnglish
Article number7894
JournalScientific reports
Volume13
Issue number1
DOIs
Publication statusPublished - 2023 Dec

All Science Journal Classification (ASJC) codes

  • General

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