Particle and Fibre Toxicology最新文献

{"title":"Correction: Combining analytical techniques to assess the translocation of diesel particles across an alveolar tissue barrier in vitro.","authors":"Gowsinth Gunasingam, Ruiwen He, Patricia Taladriz-Blanco, Sandor Balog, Alke Petri-Fink, Barbara Rothen-Rutishauser","doi":"10.1186/s12989-024-00593-7","DOIUrl":"10.1186/s12989-024-00593-7","url":null,"abstract":"","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"21 1","pages":"31"},"PeriodicalIF":7.2,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11312927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141913656","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":"Investigation of pulmonary inflammatory responses following intratracheal instillation of and inhalation exposure to polypropylene microplastics.","authors":"Taisuke Tomonaga, Hidenori Higashi, Hiroto Izumi, Chinatsu Nishida, Naoki Kawai, Kazuma Sato, Toshiki Morimoto, Yasuyuki Higashi, Kazuhiro Yatera, Yasuo Morimoto","doi":"10.1186/s12989-024-00592-8","DOIUrl":"10.1186/s12989-024-00592-8","url":null,"abstract":"<p><strong>Background: </strong>Microplastics have been detected in the atmosphere as well as in the ocean, and there is concern about their biological effects in the lungs. We conducted a short-term inhalation exposure and intratracheal instillation using rats to evaluate lung disorders related to microplastics. We conducted an inhalation exposure of polypropylene fine powder at a low concentration of 2 mg/m³ and a high concentration of 10 mg/m³ on 8-week-old male Fischer 344 rats for 6 h a day, 5 days a week for 4 weeks. We also conducted an intratracheal instillation of polypropylene at a low dose of 0.2 mg/rat and a high dose of 1.0 mg/rat on 12-week-old male Fischer 344 rats. Rats were dissected from 3 days to 6 months after both exposures, and bronchoalveolar lavage fluid (BALF) and lung tissue were collected to analyze lung inflammation and lung injury.</p><p><strong>Results: </strong>Both exposures to polypropylene induced a persistent influx of inflammatory cells and expression of CINC-1, CINC-2, and MPO in BALF from 1 month after exposure. Genetic analysis showed a significant increase in inflammation-related factors for up to 6 months. The low concentration in the inhalation exposure of polypropylene also induced mild lung inflammation.</p><p><strong>Conclusion: </strong>These findings suggest that inhaled polypropylene, which is a microplastic, induces persistent lung inflammation and has the potential for lung disorder. Exposure to 2 mg/m³ induced inflammatory changes and was thought to be the Lowest Observed Adverse Effect Level (LOAEL) for acute effects of polypropylene. However, considering the concentration of microplastics in a real general environment, the risk of environmental hazards to humans may be low.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"21 1","pages":"29"},"PeriodicalIF":7.2,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11301944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897966","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":"Worse pulmonary function in association with cumulative exposure to nanomaterials. Hints of a mediation effect via pulmonary inflammation.","authors":"Giulia Squillacioti, Thomas Charreau, Pascal Wild, Valeria Bellisario, Federica Ghelli, Roberto Bono, Enrico Bergamaschi, Giacomo Garzaro, Irina Guseva Canu","doi":"10.1186/s12989-024-00589-3","DOIUrl":"10.1186/s12989-024-00589-3","url":null,"abstract":"<p><strong>Background: </strong>Today, nanomaterials are broadly used in a wide range of industrial applications. Such large utilization and the limited knowledge on to the possible health effects have raised concerns about potential consequences on human health and safety, beyond the environmental burden. Given that inhalation is the main exposure route, workers exposed to nanomaterials might be at risk of occurrence of respiratory morbidity and/or reduced pulmonary function. However, epidemiological evidence regarding the association between cumulative exposure to nanomaterials and respiratory health is still scarce. This study focused on the association between cumulative exposure to nanomaterials and pulmonary function among 136 workers enrolled in the framework of the European multicentric NanoExplore project.</p><p><strong>Results: </strong>Our findings suggest that, independently of lifelong tobacco smoking, ethnicity, age, sex, body mass index and physical activity habits, 10-year cumulative exposure to nanomaterials is associated to worse FEV₁ and FEF_25 - 75%, which might be consistent with the involvement of both large and small airway components and early signs of airflow obstruction. We further explored the hypothesis of a mediating effect via airway inflammation, assessed by interleukin (IL-)10, IL-1β and Tumor Necrosis Factor alpha (TNF-α), all quantified in the Exhaled Breath Condensate of workers. The mediation analysis results suggest that IL-10, TNF-α and their ratio (i.e., anti-pro inflammatory ratio) may fully mediate the negative association between cumulative exposure to nanomaterials and the FEV₁/FVC ratio. This pattern was not observed for other pulmonary function parameters.</p><p><strong>Conclusions: </strong>Safeguarding the respiratory health of workers exposed to nanomaterials should be of primary importance. The observed association between cumulative exposure to nanomaterials and worse pulmonary function parameters underscores the importance of implementing adequate protective measures in the nanocomposite sector. The mitigation of harmful exposures may ensure that workers can continue to contribute productively to their workplaces while preserving their respiratory health over time.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"21 1","pages":"28"},"PeriodicalIF":7.2,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11212158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141470079","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":"Systemic immunological responses are dependent on sex and ovarian hormone presence following acute inhaled woodsmoke exposure.","authors":"Kartika Wardhani, Sydnee Yazzie, Charlotte McVeigh, Onamma Edeh, Martha Grimes, Quiteria Jacquez, Connor Dixson, Edward Barr, Rui Liu, Alicia M Bolt, Changjian Feng, Katherine E Zychowski","doi":"10.1186/s12989-024-00587-5","DOIUrl":"10.1186/s12989-024-00587-5","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Rural regions of the western United States have experienced a noticeable surge in both the frequency and severity of acute wildfire events, which brings significant challenges to both public safety and environmental conservation efforts, with impacts felt globally. Identifying factors contributing to immune dysfunction, including endocrinological phenotypes, is essential to understanding how hormones may influence toxicological susceptibility.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This exploratory study utilized male and female C57BL/6 mice as in vivo models to investigate distinct responses to acute woodsmoke (WS) exposure with a focus on sex-based differences. In a second set of investigations, two groups were established within the female mouse cohort. In one group, mice experienced ovariectomy (OVX) to simulate an ovarian hormone-deficient state similar to surgical menopause, while the other group received Sham surgery as controls, to investigate the mechanistic role of ovarian hormone presence in driving immune dysregulation following acute WS exposure. Each experimental cohort followed a consecutive 2-day protocol with daily 4-h exposure intervals under two conditions: control HEPA-filtered air (FA) and acute WS to simulate an acute wildfire episode.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Metals analysis of WS particulate matter (PM) revealed significantly increased levels of &lt;sup&gt;63&lt;/sup&gt;Cu, &lt;sup&gt;182&lt;/sup&gt;W, &lt;sup&gt;208&lt;/sup&gt;Pb, and &lt;sup&gt;238&lt;/sup&gt;U, compared to filtered air (FA) controls, providing insights into the specific metal components most impacted by the changing dynamics of wildfire occurrences in the region. Male and female mice exhibited diverse patterns in lung mRNA cytokine expression following WS exposure, with males showing downregulation and females displaying upregulation, notably for IL-1β, TNF-α, CXCL-1, CCL-5, TGF-β, and IL-6. After acute WS exposure, there were notable differences in the responses of macrophages, neutrophils, and bronchoalveolar lavage (BAL) cytokines IL-10, IL-6, IL-1β, and TNF-α. Significant diverse alterations were observed in BAL cytokines, specifically IL-1β, IL-10, IL-6, and TNF-α, as well as in the populations of immune cells, such as macrophages and polymorphonuclear leukocytes, in both Sham and OVX mice, following acute WS exposure. These findings elucidated the profound influence of hormonal changes on inflammatory outcomes, delineating substantial sex-related differences in immune activation and revealing altered immune responses in OVX mice due to ovarian hormone deficiency. In addition, the flow cytometry analysis highlighted the complex interaction between OVX surgery, acute WS exposure, and their collective impact on immune cell populations within the hematopoietic bone marrow niche.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;In summary, both male and female mice, alongside females subjected to OVX and those who had sham surgery, exhibit significant variations in the expression ","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"21 1","pages":"27"},"PeriodicalIF":7.2,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11129474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141155592","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":"Combining analytical techniques to assess the translocation of diesel particles across an alveolar tissue barrier in vitro.","authors":"Gowsinth Gunasingam, Ruiwen He, Patricia Taladriz-Blanco, Sandor Balog, Alke Petri-Fink, Barbara Rothen-Rutishauser","doi":"10.1186/s12989-024-00585-7","DOIUrl":"10.1186/s12989-024-00585-7","url":null,"abstract":"<p><strong>Background: </strong>During inhalation, airborne particles such as particulate matter ≤ 2.5 μm (PM_2.5), can deposit and accumulate on the alveolar epithelial tissue. In vivo studies have shown that fractions of PM_2.5 can cross the alveolar epithelium to blood circulation, reaching secondary organs beyond the lungs. However, approaches to quantify the translocation of particles across the alveolar epithelium in vivo and in vitro are still not well established. In this study, methods to assess the translocation of standard diesel exhaust particles (DEPs) across permeable polyethylene terephthalate (PET) inserts at 0.4, 1, and 3 μm pore sizes were first optimized with transmission electron microscopy (TEM), ultraviolet-visible spectroscopy (UV-VIS), and lock-in thermography (LIT), which were then applied to study the translocation of DEPs across human alveolar epithelial type II (A549) cells. A549 cells that grew on the membrane (pore size: 3 μm) in inserts were exposed to DEPs at different concentrations from 0 to 80 µg.mL^- 1 ( 0 to 44 µg.cm^- 2) for 24 h. After exposure, the basal fraction was collected and then analyzed by combining qualitative (TEM) and quantitative (UV-VIS and LIT) techniques to assess the translocated fraction of the DEPs across the alveolar epithelium in vitro.</p><p><strong>Results: </strong>We could detect the translocated fraction of DEPs across the PET membranes with 3 μm pore sizes and without cells by TEM analysis, and determine the percentage of translocation at approximatively 37% by UV-VIS (LOD: 1.92 µg.mL^- 1) and 75% by LIT (LOD: 0.20 µg.cm^- 2). In the presence of cells, the percentage of DEPs translocation across the alveolar tissue was determined around 1% at 20 and 40 µg.mL^- 1 (11 and 22 µg.cm^- 2), and no particles were detected at higher and lower concentrations. Interestingly, simultaneous exposure of A549 cells to DEPs and EDTA can increase the translocation of DEPs in the basal fraction.</p><p><strong>Conclusion: </strong>We propose a combination of analytical techniques to assess the translocation of DEPs across lung tissues. Our results reveal a low percentage of translocation of DEPs across alveolar epithelial tissue in vitro and they correspond to in vivo findings. The combination approach can be applied to any traffic-generated particles, thus enabling us to understand their involvement in public health.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"21 1","pages":"26"},"PeriodicalIF":7.2,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11110323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081592","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":"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/s12989-024-00572-y","DOIUrl":"10.1186/s12989-024-00572-y","url":null,"abstract":"<p><strong>Background: </strong>Significant variations exist in the forms of ZnO, making it impossible to test all forms in in vivo inhalation studies. Hence, grouping and read-across is a common approach under REACH to evaluate the toxicological profile of familiar substances. The objective of this paper is to investigate the potential role of dissolution, size, or coating in grouping ZnO (nano)forms for the purpose of hazard assessment. We performed a 90-day inhalation study (OECD test guideline no. (TG) 413) in rats combined with a reproduction/developmental (neuro)toxicity screening test (TG 421/424/426) with coated and uncoated ZnO nanoforms in comparison with microscale ZnO particles and soluble zinc sulfate. In addition, genotoxicity in the nasal cavity, lungs, liver, and bone marrow was examined via comet assay (TG 489) after 14-day inhalation exposure.</p><p><strong>Results: </strong>ZnO nanoparticles caused local toxicity in the respiratory tract. Systemic effects that were not related to the local irritation were not observed. There was no indication of impaired fertility, developmental toxicity, or developmental neurotoxicity. No indication for genotoxicity of any of the test substances was observed. Local effects were similar across the different ZnO test substances and were reversible after the end of the exposure.</p><p><strong>Conclusion: </strong>With exception of local toxicity, this study could not confirm the occasional findings in some of the previous studies regarding the above-mentioned toxicological endpoints. The two representative ZnO nanoforms and the microscale particles showed similar local effects. The ZnO nanoforms most likely exhibit their effects by zinc ions as no particles could be detected after the end of the exposure, and exposure to rapidly soluble zinc sulfate had similar effects. Obviously, material differences between the ZnO particles do not substantially alter their toxicokinetics and toxicodynamics. The grouping of ZnO nanoforms into a set of similar nanoforms is justified by these observations.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"21 1","pages":"24"},"PeriodicalIF":7.2,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11100124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140957361","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":"Determining the toxicological effects of indoor air pollution on both a healthy and an inflammatory-comprised model of the alveolar epithelial barrier in vitro.","authors":"Kirsty Meldrum, Stephen J Evans, Michael J Burgum, Shareen H Doak, Martin J D Clift","doi":"10.1186/s12989-024-00584-8","DOIUrl":"10.1186/s12989-024-00584-8","url":null,"abstract":"<p><p>Exposure to indoor air pollutants (IAP) has increased recently, with people spending more time indoors (i.e. homes, offices, schools and transportation). Increased exposures of IAP on a healthy population are poorly understood, and those with allergic respiratory conditions even less so. The objective of this study, therefore, was to implement a well-characterised in vitro model of the human alveolar epithelial barrier (A549 + PMA differentiated THP-1 incubated with and without IL-13, IL-5 and IL-4) to determine the effects of a standardised indoor particulate (NIST 2583) on both a healthy lung model and one modelling a type-II (stimulated with IL-13, IL-5 and IL-4) inflammatory response (such as asthma).Using concentrations from the literature, and an environmentally appropriate exposure we investigated 232, 464 and 608ng/cm² of NIST 2583 respectively. Membrane integrity (blue dextran), viability (trypan blue), genotoxicity (micronucleus (Mn) assay) and (pro-)/(anti-)inflammatory effects (IL-6, IL-8, IL-33, IL-10) were then assessed 24 h post exposure to both models. Models were exposed using a physiologically relevant aerosolisation method (VitroCell Cloud 12 exposure system).No changes in Mn frequency or membrane integrity in either model were noted when exposed to any of the tested concentrations of NIST 2583. A significant decrease (p < 0.05) in cell viability at the highest concentration was observed in the healthy model. Whilst cell viability in the \"inflamed\" model was decreased at the lower concentrations (significantly (p < 0.05) after 464ng/cm²). A significant reduction (p < 0.05) in IL-10 and a significant increase in IL-33 was seen after 24 h exposure to NIST 2583 (464, 608ng/cm²) in the \"inflamed\" model.Collectively, the results indicate the potential for IAP to cause the onset of a type II response as well as exacerbating pre-existing allergic conditions. Furthermore, the data imposes the importance of considering unhealthy individuals when investigating the potential health effects of IAP. It also highlights that even in a healthy population these particles have the potential to induce this type II response and initiate an immune response following exposure to IAP.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"21 1","pages":"25"},"PeriodicalIF":7.2,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11100169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140956843","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":"Synthetic silica fibers of different length, diameter and shape: synthesis and interaction with rat (NR8383) and human (THP-1) macrophages in vitro, including chemotaxis and gene expression profile.","authors":"Nataniel Białas, Nina Rosenkranz, Daniel Gilbert Weber, Kathrin Kostka, Georg Johnen, Aileen Winter, Alexander Brik, Kateryna Loza, Katja Szafranski, Thomas Brüning, Jürgen Bünger, Götz Westphal, Matthias Epple","doi":"10.1186/s12989-024-00586-6","DOIUrl":"10.1186/s12989-024-00586-6","url":null,"abstract":"<p><strong>Background: </strong>Inhalation of biopersistent fibers like asbestos can cause strong chronic inflammatory effects, often resulting in fibrosis or even cancer. The interplay between fiber shape, fiber size and the resulting biological effects is still poorly understood due to the lack of reference materials.</p><p><strong>Results: </strong>We investigated how length, diameter, aspect ratio, and shape of synthetic silica fibers influence inflammatory effects at doses up to 250 µg cm^-2. Silica nanofibers were prepared with different diameter and shape. Straight (length ca. 6 to 8 µm, thickness ca. 0.25 to 0.35 µm, aspect ratio ca. 17:1 to 32:1) and curly fibers (length ca. 9 µm, thickness ca. 0.13 µm, radius of curvature ca. 0.5 µm, aspect ratio ca. 70:1) were dispersed in water with no apparent change in the fiber shape during up to 28 days. Upon immersion in aqueous saline (DPBS), the fibers released about 5 wt% silica after 7 days irrespectively of their shape. The uptake of the fibers by macrophages (human THP-1 and rat NR8383) was studied by scanning electron microscopy and confocal laser scanning microscopy. Some fibers were completely taken up whereas others were only partially internalized, leading to visual damage of the cell wall. The biological effects were assessed by determining cell toxicity, particle-induced chemotaxis, and the induction of gene expression of inflammatory mediators.</p><p><strong>Conclusions: </strong>Straight fibers were only slightly cytotoxic and caused weak cell migration, regardless of their thickness, while the curly fibers were more toxic and caused significantly stronger chemotaxis. Curly fibers also had the strongest effect on the expression of cytokines and chemokines. This may be due to the different aspect ratio or its twisted shape.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"21 1","pages":"23"},"PeriodicalIF":7.2,"publicationDate":"2024-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11088073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140909040","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":"Cellular response of keratinocytes to the entry and accumulation of nanoplastic particles","authors":"Leisha Martin, Kayla Simpson, Molly Brzezinski, John Watt, Wei Xu","doi":"10.1186/s12989-024-00583-9","DOIUrl":"https://doi.org/10.1186/s12989-024-00583-9","url":null,"abstract":"Plastic accumulation in the environment is rapidly increasing, and nanoplastics (NP), byproducts of environmental weathering of bulk plastic waste, pose a significant public health risk. Particles may enter the human body through many possible routes such as ingestion, inhalation, and skin absorption. However, studies on NP penetration and accumulation in human skin are limited. Loss or reduction of the keratinized skin barrier may enhance the skin penetration of NPs. The present study investigated the entry of NPs into a human skin system modeling skin with compromised barrier functions and cellular responses to the intracellular accumulations of NPs. Two in vitro models were employed to simulate human skin lacking keratinized barriers. The first model was an ex vivo human skin culture with the keratinized dermal layer (stratum corneum) removed. The second model was a 3D keratinocyte/dermal fibroblast cell co-culture model with stratified keratinocytes on the top and a monolayer of skin fibroblast cells co-cultured at the bottom. The penetration and accumulation of the NPs in different cell types were observed using fluorescent microscopy, confocal microscopy, and cryogenic electron microscopy (cryo-EM). The cellular responses of keratinocytes and dermal fibroblast cells to stress induced by NPs stress were measured. The genetic regulatory pathway of keratinocytes to the intracellular NPs was identified using transcript analyses and KEGG pathway analysis. The cellular uptake of NPs by skin cells was confirmed by imaging analyses. Transepidermal transport and penetration of NPs through the skin epidermis were observed. According to the gene expression and pathway analyses, an IL-17 signaling pathway was identified as the trigger for cellular responses to internal NP accumulation in the keratinocytes. The transepidermal NPs were also found in co-cultured dermal fibroblast cells and resulted in a large-scale transition from fibroblast cells to myofibroblast cells with enhanced production of α-smooth muscle actin and pro-Collagen Ia. The upregulation of inflammatory factors and cell activation may result in skin inflammation and ultimately trigger immune responses.","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"1 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140813004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute exposure to polystyrene nanoparticles promotes liver injury by inducing mitochondrial ROS-dependent necroptosis and augmenting macrophage-hepatocyte crosstalk","authors":"Junjie Fan, Li Liu, Yongling Lu, Qian Chen, Shijun Fan, Yongjun Yang, Yupeng Long, Xin Liu","doi":"10.1186/s12989-024-00578-6","DOIUrl":"https://doi.org/10.1186/s12989-024-00578-6","url":null,"abstract":"The global use of plastic materials has undergone rapid expansion, resulting in the substantial generation of degraded and synthetic microplastics and nanoplastics (MNPs), which have the potential to impose significant environmental burdens and cause harmful effects on living organisms. Despite this, the detrimental impacts of MNPs exposure towards host cells and tissues have not been thoroughly characterized. In the present study, we have elucidated a previously unidentified hepatotoxic effect of 20 nm synthetic polystyrene nanoparticles (PSNPs), rather than larger PS beads, by selectively inducing necroptosis in macrophages. Mechanistically, 20 nm PSNPs were rapidly internalized by macrophages and accumulated in the mitochondria, where they disrupted mitochondrial integrity, leading to heightened production of mitochondrial reactive oxygen species (mtROS). This elevated mtROS generation essentially triggered necroptosis in macrophages, resulting in enhanced crosstalk with hepatocytes, ultimately leading to hepatocyte damage. Additionally, it was demonstrated that PSNPs induced necroptosis and promoted acute liver injury in mice. This harmful effect was significantly mitigated by the administration of a necroptosis inhibitor or systemic depletion of macrophages prior to PSNPs injection. Collectively, our study suggests a profound toxicity of environmental PSNP exposure by triggering macrophage necroptosis, which in turn induces hepatotoxicity via intercellular crosstalk between macrophages and hepatocytes in the hepatic microenvironment.","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"241 1","pages":""},"PeriodicalIF":10.0,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140563114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}