PM2.5 Aggravated OVA-Induced Epithelial Tight Junction Disruption Through Fas Associated via Death Domain-Dependent Apoptosis in Asthmatic Mice

He, Xiang; Zhang, Lei; Hu, Lingjuan; Liu, Shengbin; Xiong, Anying; Wang, Junyi; Xiong, Ying; Li, Guoping

doi:10.2147/jaa.s335590

Cited by 12 publications

(4 citation statements)

References 46 publications

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“…Isolated neutrophils were seeded in 96-well plates at a density of 10 5 cells per well. The cells were treated with 62 µg/cm 2 of PM2.5 [ 46 ] and 50 µg/ml of PD-L1 mAb/isotype control for a duration of 3 h. After removing the supernatant, the cells were thoroughly washed with PBS to eliminate any residual substances. Subsequently, 200 µl of cell culture medium and 20 µl of neutral red staining solution was added to each well.…”

Section: Methodsmentioning

confidence: 99%

Fine particulate matter 2.5 induces susceptibility to Pseudomonas aeruginosa infection via expansion of PD-L1high neutrophils in mice

Luo,

Jiang,

Xiong

et al. 2024

Respir Res

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Background Exposure to PM2.5 has been implicated in a range of detrimental health effects, particularly affecting the respiratory system. However, the precise underlying mechanisms remain elusive. Methods To address this objective, we collected ambient PM2.5 and administered intranasal challenges to mice, followed by single-cell RNA sequencing (scRNA-seq) to unravel the heterogeneity of neutrophils and unveil their gene expression profiles. Flow cytometry and immunofluorescence staining were subsequently conducted to validate the obtained results. Furthermore, we assessed the phagocytic potential of neutrophils upon PM2.5 exposure using gene analysis of phagocytosis signatures and bacterial uptake assays. Additionally, we utilized a mouse pneumonia model to evaluate the susceptibility of PM2.5-exposed mice to Pseudomonas aeruginosa infection. Results Our study revealed a significant increase in neutrophil recruitment within the lungs of PM2.5-exposed mice, with subclustering of neutrophils uncovering subsets with distinct gene expression profiles. Notably, exposure to PM2.5 was associated with an expansion of PD-L1high neutrophils, which exhibited impaired phagocytic function dependent upon PD-L1 expression. Furthermore, PM2.5 exposure was found to increase the susceptibility of mice to Pseudomonas aeruginosa, due in part to increased PD-L1 expression on neutrophils. Importantly, monoclonal antibody targeting of PD-L1 significantly reduced bacterial burden, dissemination, and lung inflammation in PM2.5-exposed mice upon Pseudomonas aeruginosa infection. Conclusions Our study suggests that PM2.5 exposure promotes expansion of PD-L1high neutrophils with impaired phagocytic function in mouse lungs, contributing to increased vulnerability to bacterial infection, and therefore targeting PD-L1 may be a therapeutic strategy for reducing the harmful effects of PM2.5 exposure on the immune system.

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Section: Methodsmentioning

confidence: 99%

Fine particulate matter 2.5 induces susceptibility to Pseudomonas aeruginosa infection via expansion of PD-L1high neutrophils in mice

Luo,

Jiang,

Xiong

et al. 2024

Respir Res

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“…In human bronchial epithelial cells (16HBE), PFOS disrupts epithelial integrity as early as 4 h, as indicated by decreased transepithelial electrical resistance (TEER) and increased dextran-FITC permeability ( Lucas et al, 2022 ). Additionally, PFOS exposure reduces the expression and organization of tight junction proteins, occludin and zonula occludens 1 (ZO-1), which collectively results in a breakdown of the epithelial barrier and an increase in permeability ( Li et al, 2012 ; Zhang Y. et al, 2021 ; He et al, 2021 ). In BEAS-2B cells, PFOA alters membrane potential and activates the NLRP3 inflammasome ( Dragon et al, 2023 ).…”

Section: Lung-specific Effects Of Pfas At Cellular- and Tissue-levelsmentioning

confidence: 99%

Per- and poly-fluoroalkyl substances (PFAS) effects on lung health: a perspective on the current literature and future recommendations

Solan,

Park

2024

Front. Toxicol.

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Per- and poly-fluoroalkyl substances (PFAS) are a broad class of synthetic compounds widely used in commercial applications. The persistent nature of PFAS in the environment has earned them the epithet “forever chemicals.” Concerns arise from widespread exposure to PFAS from occupational, household, and environmental sources. This widespread use of PFAS is particularly concerning, as emerging epidemiological evidence highlights their adverse effects on lung health. Such adverse impacts include impaired fetal lung development, reduced immune function in children, and potential links to lung cancer. Both in vivo and in vitro studies illuminate potential mechanisms underlying such adverse health outcomes subsequent to PFAS inhalation exposure, which may include immunomodulation, oxidative stress, and disruptions to epithelial barriers. However, evidence-based information focusing on the mechanisms of PFAS-mediated lung injury is lacking. Additionally, the discrepancies between data collected from animal and epidemiological studies highlight the need for improved approaches to better understand the toxicity results of PFAS exposure. To address these gaps, we recommend leveraging route-to-route extrapolation for risk assessment, prioritizing research on understudied PFAS, and adopting physiologically relevant, high-throughput approaches. These strategies are aimed at enhancing our understanding of PFAS inhalation effects, aiding in more informed risk management decisions. In this review, we summarize the current literature on PFAS exposure, emphasizing its adverse effects on lung health, particularly through inhalation. We then discuss the current knowledge on mechanisms underlying tissue- and cellular-level adverse outcomes caused by PFAS.

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“…For example, in vitro and in vivo experiments revealed that PM2.5 exposure influenced the severity of experimental asthma by stimulating more epithelial cell apoptosis. 32 , 33 However, the extent of pathological airway epithelial cell apoptosis in asthmatic patients is still unknown, and its importance to the pathogenesis of asthma has not been comprehensively established.…”

Section: Apoptosis In Asthmamentioning

confidence: 99%

Programmed Cell Death in Asthma: Apoptosis, Autophagy, Pyroptosis, Ferroptosis, and Necroptosis

Lü¹,

Zhou²,

Wang³

et al. 2023

JIR

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Bronchial asthma is a complex heterogeneous airway disease, which has emerged as a global health issue. A comprehensive understanding of the different molecular mechanisms of bronchial asthma may be an efficient means to improve its clinical efficacy in the future. Increasing research evidence indicates that some types of programmed cell death (PCD), including apoptosis, autophagy, pyroptosis, ferroptosis, and necroptosis, contributed to asthma pathogenesis, and may become new targets for future asthma treatment. This review briefly discusses the molecular mechanism and signaling pathway of these forms of PCD focuses on summarizing their roles in the pathogenesis and treatment strategies of asthma and offers some efficient means to improve clinical efficacy of therapeutics for asthma in the near future.

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PM2.5 Aggravated OVA-Induced Epithelial Tight Junction Disruption Through Fas Associated via Death Domain-Dependent Apoptosis in Asthmatic Mice

Cited by 12 publications

References 46 publications

Fine particulate matter 2.5 induces susceptibility to Pseudomonas aeruginosa infection via expansion of PD-L1high neutrophils in mice

Fine particulate matter 2.5 induces susceptibility to Pseudomonas aeruginosa infection via expansion of PD-L1high neutrophils in mice

Per- and poly-fluoroalkyl substances (PFAS) effects on lung health: a perspective on the current literature and future recommendations

Programmed Cell Death in Asthma: Apoptosis, Autophagy, Pyroptosis, Ferroptosis, and Necroptosis

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