The influence of PM2.5 exposure on SARS-CoV-2 infection via modulating the expression of angiotensin converting enzyme II

• Published in: Journal of hazardous materials Vol. 485; p. 136887
• Main Authors: Lin, Meng-Wei, Lin, Cheng-Han, Chang, Jia-Rong, Chiang, Hua-Hsin, Wu, Ting-Hsuan, Lin, Chih-Sheng
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 05.03.2025
• Subjects: Air Pollutants - toxicity; Air pollution; Angiotensin converting enzyme II; Angiotensin-Converting Enzyme 2 - genetics; Animals; COVID-19; Humans; Inflammation; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Pandemics; Particulate Matter - toxicity; Particulate matter 2.5; Peptidyl-Dipeptidase A - genetics; Peptidyl-Dipeptidase A - metabolism; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; NADPH; HEK293T; RAS; K18-hACE2 TG; HRP; FIRDI; MERS-CoV; MTT; COVID-19; GFP; SD; SARS-CoV-2; RRR; SARS-CoV-1; FBS; PM2.5; HEK293T-hACE2; WT; PBS; ACE; NFκB; H&E; VEGF; BALF; Inflammation; MAPK; Ang II; IL-6; Angiotensin converting enzyme II; MACE2 KO; Severe acute respiratory syndrome coronavirus 2; ACE2; DCFH-DA; TNF-α; Particulate matter 2.5; ROS; Air pollution; BLI; ELISA
• ISSN: 0304-3894; 1873-3336; 1873-3336
• DOI: 10.1016/j.jhazmat.2024.136887

Particulate matter 2.5 (PM2.5) pollution and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic are the greatest environmental health issues worldwide. Several statistics revealed the significant positive correlation between the morbidity of coronavirus disease-19 (COVID-19) and the levels of air pollution. Nevertheless, there is no direct experimental evidence to indicate the effect of PM2.5 exposure on SARS-CoV-2 infection. The objective of this study was to evaluate whether the infection of SARS-CoV-2 affected by PM2.5 through angiotensin-converting enzyme II (ACE2) expression enhances and investigate the function of ACE2 in lung injury induced by PM2.5. An animal model of PM2.5-induced lung injury was established using wild-type (WT, C57BL/6), human ACE2 transgenic (K18-hACE2 TG), and murine ACE2 gene knockout (mACE2 KO) mice. The results indicate that PM2.5 exposure facilitates SARS-CoV-2 infection through inducing ACE2 expression in vitro (10 μg/mL) and in vivo (6.25 mg/kg/day in 50 μL saline). The levels of ACE, inflammatory cytokines, and mitogen-activated protein kinase (MAPK) proteins in WT, K18-hACE TG and mACE2 KO mice were significantly increased after PM2.5 instillation. The severest PM2.5-induced lung damage was observed in mACE2 KO mice. In summary, ACE2 plays a double-edged sword role in lung injury, PM2.5 exposure contributed to SARS-CoV-2 infection through inducing ACE2 expression, but ACE2 also protected pulmonary inflammation from PM2.5 challenge. [Display omitted] •PM2.5 is a plausible environmental transmission carrier for SARS-CoV-2.•Air pollutants PM2.5 exacerbates SARS-CoV-2 infection by promoting ACE2 expression.•An ACE2 transgenic mouse model of PM2.5-induced lung injury was established.•PM2.5 instillation dysregulates the expression of renin–angiotensin system proteins.•PM2.5 activates the MAPK pathway and increases the inflammatory state.