Particle and Fibre Toxicology最新文献

{"title":"Fabrication of microplastic and nanoplastic particles and fibres for use in pulmonary toxicity studies.","authors":"Eric Auyang, Mengzheng Ouyang, Adam Laycock, Henry Blake, Teresa D Tetley, Timothy W Gant, Anne E Willis, Stephanie Wright","doi":"10.1186/s12989-025-00641-w","DOIUrl":"10.1186/s12989-025-00641-w","url":null,"abstract":"<p><strong>Background: </strong>Micro/nanoplastics (MNPs) are a commonly detected environmental contaminant in indoor and outdoor environments. Airborne MNPs are of various shapes and sizes, some of which are small enough to reach the deep lung if inhaled. Current research into the toxicity of airborne MNPs in the lung has only involved a small number of polymers and shapes due to their limited availability. The most commonly available are polystyrene spheres and to date, these have been used in the majority of studies, though their relevance to environmental MNPs is limited. To address this gap, we aimed to develop a method to fabricate MNPs of three environmentally relevant polymers, producing both micro- and nano-sized particles as well as fibres. Enhancing the consistency and accessibility of test materials will enable researchers to better investigate how size, shape, and polymer type influence lung toxicity, while also reducing variability introduced during fabrication.</p><p><strong>Results: </strong>We successfully developed methods to fabricate MNPs of polyamide, polystyrene, and polyethylene terephthalate, as microplastics, nanoplastics, and fibres. MNPs were characterized for their chemical purity and size. The size of the fabricated MNPs were found to be of a respirable dimension. As a solvent-based method of preparation was used, leachates from the MNPs were analysed to check for contamination that could cause non-specific toxicity. These were found to have no effect on the metabolic activity of either THP-1 macrophages or transformed type-1 (TT1) epithelial cells.</p><p><strong>Conclusions: </strong>This work provides pulmonary toxicologists with a method for the fabrication of MNPs and their physical and chemical characteristics. Their characteristics indicate they are a representative test material for experimental systems.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"22 1","pages":"30"},"PeriodicalIF":10.6,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12590796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145459433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A systematic review of the potential neurotoxicity of micro-and nanoplastics: the known and unknown.","authors":"Kinga Vojnits, Andrés de León, Julien Gibon, Philip Barker, Morteza Mahmoudi, Sepideh Pakpour","doi":"10.1186/s12989-025-00647-4","DOIUrl":"10.1186/s12989-025-00647-4","url":null,"abstract":"<p><strong>Background: </strong>The escalating accumulation of micro- and nanoplastics (MNPs) in the environment has raised significant concerns regarding their neurotoxic potential in vertebrates. This critical review synthesizes evidence from 234 original research articles across aquatic and terrestrial models, as well as in vitro systems, to evaluate the impacts of MNPs on the brain.</p><p><strong>Main body: </strong>Emerging data suggest that MNPs may reach the brain via olfactory translocation or by penetrating the blood-brain barrier, potentially facilitated by biomolecular corona formation. However, distribution kinetics, long-term retention, and true internal exposure levels remain unresolved. We highlight that neurotoxic outcomes, such as oxidative stress, cholinergic dysfunction, neurotransmitter imbalances, and neuronal apoptosis, vary widely depending on particle size, shape, polymer type, exposure concentration, and host species. Nevertheless, inconsistencies across models and experimental conditions, such as mismatches between oxidative stress markers and behavioral effects or lack of dose-response relationships, hinder mechanistic clarity and translational relevance to human health. Notably, most current studies employ spherical polystyrene particles at supraphysiological concentrations, limiting ecological and clinical extrapolation. Interactions with microbial biofilms and host microbiota are largely unexplored, despite their probable role in modulating neurotoxicity via the gut-brain axis. Moreover, most studies rely on analytical methods validated only for microplastic detection, while robust, standardized approaches for identifying nanoplastics in environmental and biological matrices remain lacking. These gaps hinder accurate exposure quantification, obscure tissue-specific accumulation patterns, and complicate human health risk estimation.</p><p><strong>Conclusion: </strong>To advance the field, we recommend comprehensive physicochemical characterization of MNPs, adoption of environmentally relevant exposure scenarios, inclusion of diverse polymer types and shapes, and mechanistic integration through multi-omics and adverse outcome pathway frameworks. Addressing these challenges through harmonized methodologies and interdisciplinary collaboration is essential for developing predictive models of MNP-induced neurotoxicity and informing human health risk assessments.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"22 1","pages":"29"},"PeriodicalIF":10.6,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12590691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145459483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Seasonal PM_2.5 exposures induce differential responses to influenza A virus infection in primary human airway epithelial cells.","authors":"Stephanie A Brocke, Timothy Smyth, Hong Dang, Adam Speen, Yong Ho Kim, Cara Christianson, Kasey Kovalcik, Joseph Patrick Pancras, Michael Hays, Zhen An, Weidong Wu, Ilona Jaspers","doi":"10.1186/s12989-025-00643-8","DOIUrl":"10.1186/s12989-025-00643-8","url":null,"abstract":"<p><strong>Background: </strong>Air pollution, specifically fine particulate matter (PM_2.5), in China is responsible for millions of excess deaths each decade. Examinations of Chinese municipalities have revealed correlations between ambient PM_2.5 levels and the prevalence and severity of respiratory viral infections. Seasonal sources of ambient PM_2.5 vary, with coal combustion for indoor heating significantly contributing during colder months. Due to this seasonality, we hypothesized that PM_2.5 collected in Xinxiang, China would differentially alter the response to subsequent influenza A/California/04/2009 (H1N1) viral infection in a primary human nasal epithelial cell (HNEC) culture model in a seasonality-specific manner. After the PM_2.5 samples were chemically analyzed, HNECs collected from males (N = 4) and females (N = 3) grown at air-liquid interface were exposed to 22 µg/cm² of seasonal PM_2.5 followed by inoculation with influenza A H1N1 at MOI = 0.001. At 2 and 24 h post infection (p.i.) we assessed transcriptional changes and basolateral release of immune and antiviral mediators.</p><p><strong>Results: </strong>Summer and fall PM_2.5 samples contained a greater organic carbon mass fraction compared to winter and spring. Winter contained the largest mass fraction of anionic components and spring the largest inorganic element mass fraction. Exposure to the seasonal PM_2.5 samples without infection induced a moderate transcriptional response at 2 h, with the winter PM_2.5 inducing the greatest response. The seasonal PM_2.5 exposures followed by viral infection resulted in a more robust transcriptional response at 2 h p.i. with the winter, spring, and fall PM_2.5 samples (but not the summer PM_2.5) upregulating many inflammatory pathways. At 24 h p.i., only the spring PM_2.5 sample increased inflammatory and antiviral mediator proteins in the basolateral medium, while winter PM_2.5 increased these inflammatory markers in the mock infected cultures.</p><p><strong>Conclusions: </strong>Seasonal variations in PM2.5 composition during winter, spring, and fall-coinciding with influenza season-likely enhance pro-inflammatory responses to viral infection, with early inflammation contributing to worsened pathogenesis.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"22 1","pages":"28"},"PeriodicalIF":10.6,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12570438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145401467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-omics analysis of testis after long-term exposure to polystyrene nanoplastics reveals premature testicular aging and age-dependent damage in mice.","authors":"Hongrui Feng, Yuji Huang, Hanbin Zhang, Zhiming Li, Xixian Cen, Yuge Zhuang, Xiaoyuan Zhang, Ke Ma, Shipeng Ruan, Runduan Yi, Zicong Huang, Wenyuan Liu, Maoyong Song, Zhenlie Huang, Zhenguo Chen","doi":"10.1186/s12989-025-00642-9","DOIUrl":"10.1186/s12989-025-00642-9","url":null,"abstract":"<p><strong>Background: </strong>Nanoplastics (NPs) are emerging contaminants posing significant risks to human health due to their enhanced cellular penetration. NPs have been shown to damage human testes and epididymides, impairing male fertility. However, the specific testicular damage and underlying mechanisms induced by NPs at different ages have not been thoroughly investigated.</p><p><strong>Results: </strong>In this study, we exposed young (3-month-old) and old (17-month-old) male mice to long-term (3 months) polystyrene nanoplastics (PS-NPs). The results showed that PS-NPs extensively disrupted testicular structures and functions in both age groups, leading to excessive germ cell loss, tubular degeneration, fibrosis, and declined sperm quality. Young mice exhibited premature testicular aging, while old mice showed more severe testicular damage, indicating age-dependent injury. Mechanistically, proteomics combined with Gene Ontology analysis revealed that PS-NPs primarily disturbed RNA metabolism in young mice, whereas DNA catabolism, collagen, and extracellular matrix metabolism were extensively impaired in old mice. Additionally, integrated proteomic and metabolomic analyses, along with assays conducted on primary Leydig cells, suggested that PS-NPs downregulated scavenger receptor class B type I (SR-BI), consequently impeding testosterone synthesis and aggravating testicular aging in young mice.</p><p><strong>Conclusions: </strong>Integrated with multi-omics analyses, our study collectively extends the current understanding of PS-NP-induced testicular and sperm toxicology, highlighting age- and duration-dependent risks to male reproduction. Protecting mRNA metabolism and testosterone production may help preserve reproductive capacity in young males exposed to NPs.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"22 1","pages":"27"},"PeriodicalIF":10.6,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12548188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145355715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Short-term association between ambient air pollution and heart rate variability: results from the population-based KORA S4 and FF4 studies.","authors":"Yujiao Li, Susanne Breitner-Busch, Wayne E Cascio, Siqi Zhang, Kathrin Wolf, Ina-Maria Rückert-Eheberg, Stefan Kääb, Georg Schmidt, Alexander Strom, Annette Peters, Alexandra Schneider","doi":"10.1186/s12989-025-00645-6","DOIUrl":"10.1186/s12989-025-00645-6","url":null,"abstract":"<p><strong>Background: </strong>Ambient air pollution is a major risk factor for CVDs, and a plausible mechanism is speculated to be alteration of autonomic nervous system (ANS) function. Yet, the short-term effects of air pollution on heart rate variability (HRV), a measure of ANS balance are inconsistent.</p><p><strong>Objective: </strong>This study aimed to evaluate the short-term effects of ambient PM_2.5 and NO₂ on cardiovascular autonomic function, and to determine vulnerable subgroups and temporal trends from repeated HRV and HR measurements over 14 years in the KORA cohort.</p><p><strong>Methods: </strong>We analyzed data from 4,032 participants in KORA S4 (1999-2001) and 1,912 in KORA FF4 (2013-2014). Air pollution data were from fixed monitoring stations, and HRV indices were derived from 5-minute ECG recordings. Generalized additive models (GAMs) and generalized additive mixed models (GAMMs) were used to assess associations.</p><p><strong>Results: </strong>In S4, each IQR increase in PM_2.5 at the 14-day moving average was associated with a 2.32% (95% CI: - 4.41, - 0.19) decrease in SDNN and a 1.20% (95% CI: 0.16, 2.26) increase in HR. By contrast, KORA FF4 showed opposite associations, with a 0.86% (95% CI: 0.02, 1.70) increase in SDNN at lag 4 for PM_2.5. Effect modifications by age and smoking status were observed in S4. No statistically significant associations were found in the longitudinal analysis, however, the observed trends were consistent with the effects identified in S4.</p><p><strong>Conclusion: </strong>Short-term exposure to PM_2.5 and NO₂ impacts cardiac autonomic function, with varying effects across study waves due to aging, smoking, medication, and lower pollution levels. Even at low ambient concentrations, these exposures impaired autonomic function via inflammation and oxidative stress, underscoring the importance of stringent air quality standards and lifestyle interventions in reducing cardiovascular risk.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"22 1","pages":"26"},"PeriodicalIF":10.6,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12534996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145313403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cerium dioxide nanoparticles coated with benzo[a]pyrene modify aryl hydrocarbon receptor activity, trophoblast differentiation and mitochondrial network phenotype in human placenta.","authors":"Séverine A Degrelle, Gaëlle Deval, Arnaud Tête, Claire Mikolajczak, Frank Giton, Marie-Léone Vignaud, Sonja Boland, Céline J Guigon, Xavier Coumoul, Amal Zerrad-Saadi, Marie-Pierre Golinelli-Cohen, Thierry Fournier, Ioana Ferecatu","doi":"10.1186/s12989-025-00640-x","DOIUrl":"10.1186/s12989-025-00640-x","url":null,"abstract":"<p><p>A growing body of epidemiological evidence links maternal exposure to air pollution with an increased risk of adverse pregnancy outcomes, such as preterm birth and low birth weight. Cerium dioxide nanoparticles (CeO₂ NPs or nanoceria) are emerging pollutants, used as additives in diesel fuels and cigarettes for their catalytic properties, and released into the environment. Due to their high surface-to-volume ratio and reactivity, CeO₂ NPs develop a surface coating during combustion, which may incorporate other released fuel-borne chemicals, such as benzo[a]pyrene (BaP), a known carcinogen, mutagen and reprotoxicant, raising concerns about their combined impacts on human health. To better reflect environmental reality, we produced BaP-coated CeO₂ NPs and exposed primary human trophoblasts and chorionic villi. Our findings show that BaP-coated CeO₂ NPs activate the aryl hydrocarbon receptor (AhR) pathway, enhancing trophoblast differentiation and syncytium formation, with effects distinct from those of BaP or CeO₂ NPs alone, or their unbound mixture. Additionally, exposure to CeO₂ NPs alone altered homeostasis of mitochondria, affecting their phenotype and function. While individual exposures or BaP-coated CeO₂ NPs had no detectable impact, parallel co-exposure resulted in a slight but significant reduction in basal respiration. Finally, uncoated CeO₂ NPs altered placental steroidogenesis, increasing estrone level while decreasing dehydroepiandrosterone level, with sex-specific effects. These findings suggest that CeO₂ NPs can influence the biological effects of BaP in the human placenta, including modulating trophoblast differentiation, as well as disrupting mitochondria homeostasis and steroid production, with potential implications for pregnancy outcomes in polluted environments.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"22 1","pages":"25"},"PeriodicalIF":10.6,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12522366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145293302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Toxicological inhalation studies in rats to substantiate grouping of zinc oxide nanoforms.","authors":"Tizia Thoma, Lan Ma-Hock, Steffen Schneider, Naveed Honarvar, Silke Treumann, Sibylle Groeters, Volker Strauss, Heike Marxfeld, Dorothee Funk-Weyer, Svenja Seiffert, Wendel Wohlleben, Martina Dammann, Karin Wiench, Noömi Lombaert, Christine Spirlet, Marie Vasquez, Nicole Dewhurst, Robert Landsiedel","doi":"10.1186/s12989-025-00635-8","DOIUrl":"10.1186/s12989-025-00635-8","url":null,"abstract":"","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"22 1","pages":"24"},"PeriodicalIF":8.2,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12403266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144964076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurometabolomic impacts of wood smoke and protective benefits of anti-aging therapeutics in aged female C57BL/6J mice.","authors":"David Scieszka, Jonathan Hulse, Haiwei Gu, Amanda Barkley-Levenson, Ed Barr, Marcus Garcia, Jessica G Begay, Guy Herbert, Mark McCormick, Jonathan Brigman, Andrew Ottens, Barry Bleske, Kiran Bhaskar, Matthew J Campen","doi":"10.1186/s12989-025-00639-4","DOIUrl":"10.1186/s12989-025-00639-4","url":null,"abstract":"<p><strong>Background: </strong>Wildland fires in the United States have increased in frequency and scale over the past 30 years exposing millions of people to hazardous air pollutants. Among others, aging individuals are particularly vulnerable to the effects of wildfire smoke. In this study, we assessed the neurobiological impacts of wood smoke (WS) on aged mice and the potential of anti-aging therapeutics to mitigate these impacts.</p><p><strong>Methods: </strong>Female C57BL/6 J mice, aged 18 months, were divided into 10 groups and exposed to either filtered air (FA; 5 groups) or biomass derived WS (5 groups) for 4 h/day, every other day, for 14 days (7 exposures total) with an average particulate matter (PM) concentration of 448 µg/m³ per exposure. One FA control group and one WS exposed group were euthanized 24 h after the last exposure. The remaining 8 groups (4 FA and 4 WS exposed) were treated with either vehicle control, resveratrol and nicotinamide mononucleotide (RNMN), dasatinib and quercetin (DQ), or both RNMN and DQ (RNDQ) for 10 weeks.</p><p><strong>Results: </strong>A significant reduction in NAD + within the prefrontal cortex was observed following the 14-day exposure to WS along with a reduction in serotonin. Serotonin reductions were observed up to 10 weeks post-exposure and co-occurred with neuroinflammation and behavioral alterations, including increased immobility in a forced swim test. RNMN conferred the greatest mitigating effect after WS exposure, while RNDQ treatment resulted in an upregulation of markers associated with aging in the brain. While the metabolic shift in the PFC following WS exposure was relatively modest, mice exposed to FA and vehicle control (10 weeks of natural aging) exhibited the greatest metabolic shift, including perturbed nicotinamide metabolism.</p><p><strong>Conclusion: </strong>Taken together, these findings highlight that subacute (14-day) exposure to WS results in persistent neurometabolomic and behavioral alterations in an aged mouse model and that intervention with RNMN may be a useful strategy to mitigate the adverse neurological outcomes observed. Further studies are needed to assess the specific impact of either resveratrol or NMN in isolation and to fully elucidate age-specific, as well as sex- and species-determinant, WS exposure response pathways.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"22 1","pages":"23"},"PeriodicalIF":10.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12400709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144964054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Pulmonary effects of exposure to indium and its compounds: cross-sectional survey of exposed workers and experimental findings in rodents.","authors":"Nan Liu, Yi Guan, Yan Yu, Gai Li, Ling Xue, Weikang Li, Xiaoyu Qu, Ning Li, Sanqiao Yao","doi":"10.1186/s12989-025-00634-9","DOIUrl":"10.1186/s12989-025-00634-9","url":null,"abstract":"","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"22 1","pages":"22"},"PeriodicalIF":8.2,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12345106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144837216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combustion products of burn pit constituents induce more changes in asthmatic than non-asthmatic murine lungs.","authors":"Lanazha Belfield-Simpson, Jessica R Martin, Matthew K McPeek, Alessandra Livraghi-Butrico, Hong Dang, Yong Ho Kim, M Ian Gilmour, Claire M Doerschuk","doi":"10.1186/s12989-025-00625-w","DOIUrl":"10.1186/s12989-025-00625-w","url":null,"abstract":"<p><strong>Background: </strong>Burn pits, a method for disposal of military waste outside the United States, produce toxic substances, to which 3.5 million military personnel have been and continue to be exposed. Mild asthma (persistent or intermittent symptoms of asthma but no change in pulmonary function tests) is found among military personnel. We investigated whether burn pit combustion products (CPs) are more detrimental to the airways of asthmatic than non-asthmatic mice.</p><p><strong>Methods: </strong>Mice were exposed to house dust mite antigen (HDM) or phosphate-buffered saline (PBS) 5 times over 2 weeks to initiate asthma-like airway injury. Condensates of CPs or saline were generated by flaming combustion of military cardboard, plastic and military plywood. CPs were aspirated oropharyngeally at 24 h after the final HDM or PBS instillation. The lungs were studied 24 h later.</p><p><strong>Results: </strong>HDM increased recruitment of eosinophils and mucus projection, both Muc5ac and Muc5b mRNAs and protein. Following exposure to CPs, mice exposed to HDM had a greater inflammatory response and injury, as measured by increased neutrophil recruitment and the concentration of protein in the bronchoalveolar lavage (BAL), than control mice exposed to PBS. Expression of neutrophil chemokines was enhanced. CPs had no effect on HDM-induced eosinophil recruitment or expression of Th2 cytokines. CPs had no effect on mucus production in PBS or HDM mice. However, CPs increased intraluminal mucus, as revealed by AB-PAS staining, only in HDM mice, suggesting that CPs impaired mucociliary clearance (MCC), the lung's primary defense system, only in asthmatic airways. Lung RNA sequencing revealed that CPs increased genes and gene pathways describing inflammatory processes and impaired structure and function of cilia to a greater degree in HDM mice.</p><p><strong>Conclusions: </strong>These data indicate that asthmatic mice are more susceptible to CP-induced lung remodeling and dysfunction than non-asthmatic mice. Enhanced chemokine expression suggests that the CXCL1,2,5/CXCR2 axis may be the mechanism of the increased neutrophil recruitment. A potential mechanism of mucus accumulation is that inhalation of CPs amplifies the changes in cilia and MCC caused by asthma and triggers a positive feedback loop of enhanced inflammation induced by this accumulating mucus.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"22 1","pages":"21"},"PeriodicalIF":10.6,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12305933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144743943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}