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. 2023 Apr 18;86(8):246-262.
doi: 10.1080/15287394.2023.2184738. Epub 2023 Mar 1.

VSports注册入口 - Short-term exposure of female BALB/cJ mice to e-cigarette aerosol promotes neutrophil recruitment and enhances neutrophil-platelet aggregation in pulmonary microvasculature

Hunter T Snoderly  1 , Hassan Alkhadrawi  1 , Dhruvi M Panchal  1 , Kelly L Weaver  2 , Jenna N Vito  1 , Kasey A Freshwater  1 , Stell P Santiago  3 , I Mark Olfert  4   5   6 , Timothy R Nurkiewicz  4   6 , Margaret F Bennewitz  1   4
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Short-term exposure of female BALB/cJ mice to e-cigarette aerosol promotes neutrophil recruitment and enhances neutrophil-platelet aggregation in pulmonary microvasculature (VSports最新版本)

Hunter T Snoderly et al. J Toxicol Environ Health A. .

VSports手机版 - Abstract

Despite the perception that e-cigarettes are safer than conventional cigarettes, numerous findings demonstrated that e-cigarette aerosol (EC) exposure induced compromised immune functionality, vascular changes even after acute exposure, and lung injury. Notably, altered neutrophil functionality and platelet hemodynamics have been observed post-EC exposure. It was hypothesized that EC exposure initiates an inflammatory response resulting in altered neutrophil behavior and increased neutrophil-platelet interaction in the pulmonary microvasculature. Neutrophil and platelet responses were examined up to 48 hrs following whole-body, short-term EC exposure without flavorants or nicotine in a murine model, which most closely modeled secondhand exposure. This study is the first to investigate the impact of EC exposure through lung intravital imaging. Compared to room air-exposed mice, EC-exposed mice displayed significantly increased 1. 7‒1. 9-fold number of neutrophils in the pulmonary microvasculature associated with no marked change in neutrophils within whole blood or bronchoalveolar lavage fluid (BALF). Neutrophil-platelet interactions were also significantly elevated 1. 9‒2. 5-fold in exposed mice. Plasma concentration of myeloperoxidase was markedly reduced 1 VSports手机版. 5-fold 48 hr following exposure cessation, suggesting suppressed neutrophil antimicrobial activity. Cytokine expression exhibited changes indicating vascular damage. Effects persisted for 48 hr post-EC exposure. Data demonstrated that EC exposure repeated for 3 consecutive days in 2. 5 hr intervals in the absence of flavorants or nicotine resulted in modified pulmonary vasculature hemodynamics, altered immune functionality, and a pro-inflammatory state in female BALB/cJ mice. .

Keywords: E-cigarette; ROS; microvasculature; neutrophil extracellular traps; neutrophils; platelets; vaping. V体育安卓版.

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Conflict of interest statement

Declaration of interest statement

The authors report there are no competing interests to declare.

Figures

Figure 1.
Figure 1.
Simplified exposure schema and representative EC delivery and generation conditions. A) A whole-body exposure system was used to expose mice to EC. B) The atomizer was fired for 5 sec every 60 sec, with corresponding particle concentration increases noted in the inhalation chamber’s outflow line at each puff (5 representative “puffs” are shown). C) The atomizer was run at 30W when fired (1 representative “puff” is shown).
Figure 2.
Figure 2.
Intravital confocal lung imaging reveals increased neutrophil presence, occlusive neutrophil-platelet aggregates, and thrombi in the pulmonary microvasculature of EC-exposed mice. Representative fluorescent fields of view (FOVs) from A) mice exposed to room air (RA); B) EC-exposed mice immediately after exposure (t0); C) approximately 24 hr following exposure (t24); or D) approximately 48 hr following exposure (t48) are shown. At least 15 FOVs containing venule/arteriole-capillary interfaces were randomly collected from n=5 mice per group. Neutrophils shown in blue, platelets in pink, vasculature in green, and cell-free DNA in red. Arrows indicate blood flow direction. Red circles show neutrophil-platelet aggregates which included two or more neutrophils. Areas of SYTOX staining outside the focal plane, or SYTOX+ objects outside of the bounds of the vasculature were considered as general cell-free DNA rather than true intravascular NETs. Scale bars 20 μm. See supplementary videos 1–4 for short intravital clips of each FOV shown here.
Figure 3.
Figure 3.
Quantification of intravital lung imaging FOVs reveals significantly and persistently increased neutrophil presence and neutrophil-platelet interaction in EC-exposed mice. A) Total neutrophil count, B) platelet area, and C) neutrophil-platelet aggregate area were measured using Nikon General Analysis software across all FOVs. D) NET analysis was conducted by randomly selecting 10 intravital FOVs per mouse across all groups and manually counting NETs. *indicates p<0.05 using nested one-way ANOVA with Holm-Šídák correction for multiple comparisons to RA-exposed mice.
Figure 4.
Figure 4.
Increases, though not statistically significant, were observed in key immune populations in blood (A-D) and BALF (E-H) from EC-exposed mice. Neutrophils (A,E), lymphocytes (B,F), monocytes (C, G), platelets (D), and total white blood cells (H) were counted with a ProCyte Dx Hematology analyzer. No significance relative to RA-exposed mice was detected via one-way ANOVA with Holm- Šídák correction, or when comparing RA-exposed mice to all EC-exposed mice via two-tailed Student’s t-test. Error bars SEM.
Figure 5.
Figure 5.
NET component MPO, though not DNA, was significantly reduced in EC-exposed mouse plasma at t48 (A), but not in BALF (B). DNA concentration did not change significantly with EC exposure in plasma (C) or BALF (D). * indicates p<0.05. One-way ANOVA with Holm- Šídák correction relative to RA-exposed mice was used for multiple comparisons. Error bars SEM.
Figure 6.
Figure 6.
ROS was decreased in EC-exposed plasma of EC-exposed mice. This was not significant when comparing groups to RA-exposed mice using one-way ANOVA with Holm- Šídák correction. Further, no significance was detected when comparing all ECV-exposed mice to RA-exposed mice via two-tailed student’s t-test. Error bars SEM.
Figure 7.
Figure 7.
EC exposure modified cytokine expression in plasma. Altered cytokines in EC-exposed mouse plasma (n=3 mice per membrane) were plotted as % change in pixel density relative to RA-exposed mouse plasma (n=3 mice). Only cytokines with changes ≥ 10% were plotted. * indicates p<0.05, using one-way ANOVA with Holm-Šídák correction. Error bars SEM.
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References

    1. Beklen A, and Uckan D. 2021. Electronic cigarette liquid substances propylene glycol and vegetable glycerin induce an inflammatory response in gingival epithelial cells. Human & Experimental Toxicology 40: 25–34. - PubMed
    1. Bennewitz MF, Watkins SC, and Sundd P. 2014. Quantitative intravital two-photon excitation microscopy reveals absence of pulmonary vaso-occlusion in unchallenged sickle cell disease mice. Intravital 3: e29748. - PMC - PubMed
    1. Bhat TA, Kalathil SG, Bogner PN, Blount BC, Goniewicz ML, and Thanavala YM 2020. An animal model of inhaled vitamin E acetate and EVALI-like lung injury. New England Journal of Medicine 382: 1175–1177. - PMC - PubMed
    1. Blount BC, Karwowski MP, Shields PG, Morel-Espinosa M, Valentin-Blasini L, Gardner M, Braselton M, Brosius CR, Caron KT, and Chambers D. 2020. Vitamin E acetate in bronchoalveolar-lavage fluid associated with EVALI. New England Journal of Medicine 382: 697–705. - V体育平台登录 - PMC - PubMed
    1. Bracken-Clarke D, Kapoor D, Baird AM, Buchanan PJ, Gately K, Cuffe S, and Finn SP 2021. Vaping and lung cancer–A review of current data and recommendations. Lung Cancer 153: 11–20. - V体育ios版 - PubMed

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