scholarly journals Combustible and electronic cigarette exposures increase ACE2 activity and SARS-CoV-2 Spike binding

2021 ◽  
Author(s):  
Arunava Ghosh ◽  
Vishruth Girish ◽  
Monet Lou Yuan ◽  
Raymond D. Coakley ◽  
Neil E. Alexis ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
Bronchoalveolar Lavage Fluid ◽  
Electronic Cigarettes ◽  
Lavage Fluid ◽  
Tobacco Product ◽  
Cigarette Smoke Condensate ◽  
Bronchial Epithelial ◽  
Angiotensin Converting Enzyme 2 ◽  
Epithelial Cultures ◽  
Immune Changes

The outbreak of coronavirus disease 2019 (COVID-19) has extensively impacted global health. The causative pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), binds to the angiotensin-converting enzyme 2 (ACE2) receptor, a transmembrane metallo-carboxypeptidase that is expressed in both membrane-anchored (mACE2) and soluble (sACE2) forms in the lung. Tobacco use has been speculated as a vulnerability factor for contracting SARS-CoV-2 infection and subsequent disease severity, whilst electronic cigarettes (e-cigarettes) have been shown to induce harmful proteomic and immune changes in the lungs of vapers. We therefore tested the hypothesis that combustible tobacco (e.g. cigarettes) and non-combustible e-cigarettes could affect ACE2 activity and subsequent SARS-CoV-2 infection. We observed that sACE2 activity was significantly higher in bronchoalveolar lavage fluid from both smokers and vapers compared to age-matched non-smokers. Exposure to cigarette smoke increased ACE2 levels, mACE2 activity, and sACE2 in primary bronchial epithelial cultures. Finally, treatment with either cigarette smoke condensate or JUUL e-liquid increased infections with a spike-coated SARS-CoV-2 pseudovirus. Overall, these observations suggest that tobacco product use elevates ACE2 activity and increases the potential for SARS-CoV-2 infection through enhanced spike protein binding.

scholarly journals Cigarette smoke-induced necroptosis and DAMP release trigger neutrophilic airway inflammation in mice

2016 ◽  
Vol 310 (4) ◽  
pp. L377-L386 ◽  
Author(s):  
Simon D. Pouwels ◽  
G. Jan Zijlstra ◽  
Marco van der Toorn ◽  
Laura Hesse ◽  
Renee Gras ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Airway Inflammation ◽  
Cigarette Smoke ◽  
Bronchoalveolar Lavage Fluid ◽  
Membrane Integrity ◽  
Lavage Fluid ◽  
Chronic Obstructive ◽  
Bronchial Epithelial ◽  
Proinflammatory Mediators

Recent data indicate a role for airway epithelial necroptosis, a regulated form of necrosis, and the associated release of damage-associated molecular patterns (DAMPs) in the development of chronic obstructive pulmonary disease (COPD). DAMPs can activate pattern recognition receptors (PRRs), triggering innate immune responses. We hypothesized that cigarette smoke (CS)-induced epithelial necroptosis and DAMP release initiate airway inflammation in COPD. Human bronchial epithelial BEAS-2B cells were exposed to cigarette smoke extract (CSE), and necrotic cell death (membrane integrity by propidium iodide staining) and DAMP release (i.e., double-stranded DNA, high-mobility group box 1, heat shock protein 70, mitochondrial DNA, ATP) were analyzed. Subsequently, BEAS-2B cells were exposed to DAMP-containing supernatant of CS-induced necrotic cells, and the release of proinflammatory mediators [C-X-C motif ligand 8 (CXCL-8), IL-6] was evaluated. Furthermore, mice were exposed to CS in the presence and absence of the necroptosis inhibitor necrostatin-1, and levels of DAMPs and inflammatory cell numbers were determined in bronchoalveolar lavage fluid. CSE induced a significant increase in the percentage of necrotic cells and DAMP release in BEAS-2B cells. Stimulation of BEAS-2B cells with supernatant of CS-induced necrotic cells induced a significant increase in the release of CXCL8 and IL-6, in a myeloid differentiation primary response gene 88-dependent fashion. In mice, exposure of CS increased the levels of DAMPs and numbers of neutrophils in bronchoalveolar lavage fluid, which was statistically reduced upon treatment with necrostatin-1. Together, we showed that CS exposure induces necrosis of bronchial epithelial cells and subsequent DAMP release in vitro, inducing the production of proinflammatory cytokines. In vivo, CS exposure induces neutrophilic airway inflammation that is sensitive to necroptosis inhibition.

scholarly journals A role for bronchial epithelial autotaxin in ventilator-induced lung injury

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Ioanna Nikitopoulou ◽  
Ioanna Ninou ◽  
Nikolaos Manitsopoulos ◽  
Ioanna Dimopoulou ◽  
Stylianos E. Orfanos ◽  
...  
Keyword(s):  
Lung Injury ◽  
Protein Concentration ◽  
Bronchoalveolar Lavage Fluid ◽  
Pulmonary Inflammation ◽  
Small Animal ◽  
Lavage Fluid ◽  
Bronchial Epithelial ◽  
Ventilator Induced Lung Injury ◽  
Lung Histopathology ◽  
Genetic Deletion

Abstract Background The pathophysiology of acute respiratory distress syndrome (ARDS) may eventually result in heterogeneous lung collapse and edema-flooded airways, predisposing the lung to progressive tissue damage known as ventilator-induced lung injury (VILI). Autotaxin (ATX; ENPP2), the enzyme largely responsible for extracellular lysophosphatidic acid (LPA) production, has been suggested to play a pathogenic role in, among others, pulmonary inflammation and fibrosis. Methods C57BL/6 mice were subjected to low and high tidal volume mechanical ventilation using a small animal ventilator: respiratory mechanics were evaluated, and plasma and bronchoalveolar lavage fluid (BALF) samples were obtained. Total protein concentration was determined, and lung histopathology was further performed Results Injurious ventilation resulted in increased BALF levels of ATX. Genetic deletion of ATX from bronchial epithelial cells attenuated VILI-induced pulmonary edema. Conclusion ATX participates in VILI pathogenesis.

Curcumin attenuates elastase- and cigarette smoke-induced pulmonary emphysema in mice

2009 ◽  
Vol 296 (4) ◽  
pp. L614-L623 ◽  
Author(s):  
Masaru Suzuki ◽  
Tomoko Betsuyaku ◽  
Yoko Ito ◽  
Katsura Nagai ◽  
Nao Odajima ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Cigarette Smoke ◽  
Pulmonary Emphysema ◽  
Bronchoalveolar Lavage Fluid ◽  
Pulmonary Inflammation ◽  
Antioxidant Properties ◽  
Lavage Fluid ◽  
Curcumin Treatment ◽  
Air Space ◽  
Antioxidant Gene Expression

Curcumin, a yellow pigment obtained from turmeric ( Curcumina longa), is a dietary polyphenol that has been reported to possess anti-inflammatory and antioxidant properties. The effect of curcumin against the development of pulmonary emphysema in animal models is unknown. The aim of this study was to determine whether curcumin is able to attenuate the development of pulmonary emphysema in mice. Nine-week-old male C57BL/6J mice were treated with intratracheal porcine pancreatic elastase (PPE) or exposed to mainstream cigarette smoke (CS) (60 min/day for 10 consecutive days or 5 days/wk for 12 wk) to induce pulmonary inflammation and emphysema. Curcumin (100 mg/kg) or vehicle was administrated daily by oral gavage 1 h and 24 h before intratracheal PPE treatment and daily thereafter throughout a 21-day period in PPE-exposed mice and 1 h before each CS exposure in CS-exposed mice. As a result, curcumin treatment significantly inhibited PPE-induced increase of neutrophils in bronchoalveolar lavage fluid at 6 h and on day 1 after PPE administration, with an increase in antioxidant gene expression at 6 h and significantly attenuated PPE-induced air space enlargement on day 21. It was also found that curcumin treatment significantly inhibited CS-induced increase of neutrophils and macrophages in bronchoalveolar lavage fluid after 10 consecutive days of CS exposure and significantly attenuated CS-induced air space enlargement after 12 wk of CS exposure. In conclusion, oral curcumin administration attenuated PPE- and CS-induced pulmonary inflammation and emphysema in mice.

PAF mediates cigarette smoke-induced goblet cell metaplasia in guinea pig airways

2001 ◽  
Vol 280 (3) ◽  
pp. L436-L441 ◽  
Author(s):  
Masashi Komori ◽  
Hiromasa Inoue ◽  
Koichiro Matsumoto ◽  
Hiroshi Koto ◽  
Satoru Fukuyama ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Cigarette Smoke ◽  
Goblet Cell ◽  
Bronchoalveolar Lavage Fluid ◽  
Goblet Cells ◽  
Lavage Fluid ◽  
Cigarette Smoke Exposure ◽  
Airway Diseases ◽  
Paf Receptor ◽  
Goblet Cell Metaplasia

Goblet cell metaplasia is an important morphological feature in the airways of patients with chronic airway diseases; however, the precise mechanisms that cause this feature are unknown. We investigated the role of endogenous platelet-activating factor (PAF) in airway goblet cell metaplasia induced by cigarette smoke in vivo. Guinea pigs were exposed repeatedly to cigarette smoke for 14 consecutive days. The number of goblet cells in each trachea was determined with Alcian blue-periodic acid-Schiff staining. Differential cell counts and PAF levels in bronchoalveolar lavage fluid were also evaluated. Cigarette smoke exposure significantly increased the number of goblet cells. Eosinophils, neutrophils, and PAF levels in bronchoalveolar lavage fluid were also significantly increased after cigarette smoke. Treatment with a specific PAF receptor antagonist, E-6123, significantly attenuated the increases in the number of airway goblet cells, eosinophils, and neutrophils observed after cigarette smoke exposure. These results suggest that endogenous PAF may play a key role in goblet cell metaplasia induced by cigarette smoke and that potential roles exist for inhibitors of PAF receptor in the treatment of hypersecretory airway diseases.

scholarly journals Comparison of the effects of e-cigarette vapor with cigarette smoke on lung function and inflammation in mice

2018 ◽  
Vol 315 (5) ◽  
pp. L662-L672 ◽  
Author(s):  
Constantinos Glynos ◽  
Sofia-Iris Bibli ◽  
Paraskevi Katsaounou ◽  
Athanasia Pavlidou ◽  
Christina Magkou ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cigarette Smoke ◽  
Inflammatory Responses ◽  
Electronic Cigarettes ◽  
Ambient Air ◽  
Lavage Fluid ◽  
Pulmonary Mechanics ◽  
Tissue Elasticity ◽  
Stress Markers

Electronic cigarettes (e-cigs) are advertised as a less harmful nicotine delivery system or as a new smoking cessation tool. We aimed to assess the in vivo effects of e-cig vapor in the lung and to compare them to those of cigarette smoke (CS). We exposed C57BL/6 mice for either 3 days or 4 wk to ambient air, CS, or e-cig vapor containing 1) propylene glycol/vegetable glycerol (PG:VG-Sol; 1:1), 2) PG:VG with nicotine (G:VG-N), or 3) PG:VG with nicotine and flavor (PG:VG-N+F) and determined oxidative stress, inflammation, and pulmonary mechanics. E-cig vapors, especially PG:VG-N+F, increased bronchoalveolar lavage fluid (BALF) cellularity, Muc5ac production, as well as BALF and lung oxidative stress markers at least comparably and in many cases more than CS. BALF protein content at both time points studied was only elevated in the PG:VG-N+F group. After 3 days, PG:VG-Sol altered tissue elasticity, static compliance, and airway resistance, whereas after 4 wk CS was the only treatment adversely affecting these parameters. Airway hyperresponsiveness in response to methacholine was increased similarly in the CS and PG:VG-N+F groups. Our findings suggest that exposure to e-cig vapor can trigger inflammatory responses and adversely affect respiratory system mechanics. In many cases, the added flavor in e-cigs exacerbated the detrimental effects of e-cig vapor. We conclude that both e-cig vaping and conventional cigarette smoking negatively impact lung biology.

scholarly journals FH535 Potentiation of Cigarette Smoke Condensate Cytotoxicity is Associated With Changes in β-Catenin and EGR-1 Signaling

2012 ◽  
Vol 31 (4) ◽  
pp. 380-389 ◽  
Author(s):  
William W. Polk
Keyword(s):  
Cigarette Smoke ◽  
Epithelial To Mesenchymal Transition ◽  
Target Genes ◽  
Protein Localization ◽  
Bronchial Epithelial Cell ◽  
Nuclear Accumulation ◽  
Epithelial Cell Line ◽  
Cigarette Smoke Condensate ◽  
Bronchial Epithelial ◽  
Mesenchymal Transition

Cigarette smoke condensate (CSC) has been reported to elicit morphological and transcriptional changes that suggest epithelial-to-mesenchymal transition (EMT) in cultured bronchial epithelial cells. The transdifferentiation potential of acute and prolonged CSC exposure alone or in combination with the β-catenin inhibitor, FH535, was investigated in the bronchial epithelial cell line, BEAS-2B, through assessment of cell morphology, transcript expression, protein expression, and protein localization. Changes in morphology, β-catenin translocation, E-cadherin expression, metalloproteinase expression, and fibronectin could be demonstrated independent of molecular or physiological evidence of EMT. FH535 was shown to increase CSC-induced cytotoxicity and depress β-catenin expression. However, FH535 effects were not limited to the β-catenin pathway as it also blocked the expression of early growth responsive protein 1 (EGR-1) target genes, fibronectin and phosphatase and tensin homologue, without affecting EGR-1 nuclear accumulation.

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