RESUMEN
The prevalence of allergic diseases is constantly increasing since few decades. Anthropogenic ultrafine particles (UFPs) and allergenic aerosols is highly involved in this increase; however, the underlying cellular mechanisms are not yet understood. Studies observing these effects focused mainly on singular in vivo or in vitro exposures of single particle sources, while there is only limited evidence on their subsequent or combined effects. Our study aimed at evaluating the effect of subsequent exposures to allergy-related anthropogenic and biogenic aerosols on cellular mechanism exposed at air-liquid interface (ALI) conditions. Bronchial epithelial BEAS-2B cells were exposed to UFP-rich combustion aerosols for 2 h with or without allergen pre-exposure to birch pollen extract (BPE) or house dust mite extract (HDME). The physicochemical properties of the generated particles were characterized by state-of-the-art analytical instrumentation. We evaluated the cellular response in terms of cytotoxicity, oxidative stress, genotoxicity, and in-depth gene expression profiling. We observed that single exposures with UFP, BPE, and HDME cause genotoxicity. Exposure to UFP induced pro-inflammatory canonical pathways, shifting to a more xenobiotic-related response with longer preincubation time. With additional allergen exposure, the modulation of pro-inflammatory and xenobiotic signaling was more pronounced and appeared faster. Moreover, aryl hydrocarbon receptor (AhR) signaling activation showed to be an important feature of UFP toxicity, which was especially pronounced upon pre-exposure. In summary, we were able to demonstrate the importance of subsequent exposure studies to understand realistic exposure situations and to identify possible adjuvant allergic effects and the underlying molecular mechanisms.
Asunto(s)
Contaminantes Atmosféricos , Hipersensibilidad , Humanos , Material Particulado/análisis , Contaminantes Atmosféricos/química , Alérgenos/toxicidad , Xenobióticos , Células Epiteliales/metabolismo , Aerosoles/toxicidad , Tamaño de la PartículaRESUMEN
Particularly since the wide-ranging health effects of asbestos exposure became known, great emphasis has been placed on detailed toxicity testing of known but also newly developed fiber materials. Exposure to respirable pollutants like fibers can lead to tissue injury causing lung diseases such as pulmonary fibrosis or cancer. In order to detect the toxic potential of such aerosols at an early stage, the development of suitable test systems is essential. In this study, we illustrate the development of an advanced in vitro cell model closely resembling the physiological structure of the alveoli, and we highlight its advantages over simpler models to predict pro-fibrotic changes. For this reason, we analyzed the cytotoxic effects of fiber-like multi-walled carbon nanotubes after 24 and 48 h exposure, and we investigated inflammatory, genotoxic and pro-fibrotic changes occurring in the developed triple culture consisting of lung epithelial cells, macrophages and fibroblasts compared to a co-culture of epithelial cells and fibroblasts or a mono culture of epithelial cells. In summary, the triple culture system is more precisely able to detect a pro-fibrotic phenotype including epithelial-mesenchymal transition as well as secondary genotoxicity, even if exhibiting lower cytotoxicity in contrast to the less advanced systems. These effects might be traced back to the complex interplay between the different cell types, all of which play an important role in the inflammatory response, which precedes wound healing, or even fibrosis or cancer development.
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Nanotubos de Carbono , Fibrosis Pulmonar , Humanos , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/metabolismo , Nanotubos de Carbono/toxicidad , Nanotubos de Carbono/química , Aerosoles y Gotitas Respiratorias , Pulmón , Comunicación CelularRESUMEN
Ultrafine particles (UFP) are the smallest atmospheric particulate matter linked to air pollution-related diseases. The extent to which UFP's physical and chemical properties contribute to its toxicity remains unclear. It is hypothesized that UFP act as carriers for chemicals that drive biological responses. This study explores robust methods for generating reference UFP to understand these mechanisms and perform toxicological tests. Two types of combustion-related UFP with similar elemental carbon cores and physical properties but different organic loads were generated and characterized. Human alveolar epithelial cells were exposed to these UFP at the air-liquid interface, and several toxicological endpoints were measured. UFP were generated using a miniCAST under fuel-rich conditions and immediately diluted to minimize agglomeration. A catalytic stripper and charcoal denuder removed volatile gases and semi-volatile particles from the surface. By adjusting the temperature of the catalytic stripper, UFP with high and low organic content was produced. These reference particles exhibited fractal structures with high reproducibility and stability over a year, maintaining similar mass and number concentrations (100⯵g/m3, 2.0·105 #/cm3) and a mean particle diameter of about 40â¯nm. High organic content UFP had significant PAH levels, with benzo[a]pyrene at 0.2â¯% (m/m). Toxicological evaluations revealed that both UFP types similarly affected cytotoxicity and cell viability, regardless of organic load. Higher xenobiotic metabolism was noted for PAH-rich UFP, while reactive oxidation markers increased when semi-volatiles were stripped off. Both UFP types caused DNA strand breaks, but only the high organic content UFP induced DNA oxidation. This methodology allows modification of UFP's chemical properties while maintaining comparable physical properties, linking these variations to biological responses.
RESUMEN
Building demolition following domestic fires or abrasive processing after thermal recycling can release particles harmful for the environment and human health. To mimic such situations, particles release during dry-cutting of construction materials was investigated. A reinforcement material consisting of carbon rods (CR), carbon concrete composite (C³) and thermally treated C³ (ttC³) were physicochemically and toxicologically analyzed in monocultured lung epithelial cells, and co-cultured lung epithelial cells and fibroblasts at the air-liquid interface. C³ particles reduced their diameter to WHO fibre dimensions during thermal treatment. Caused by physical properties or by polycyclic aromatic hydrocarbons and bisphenol A found in the materials, especially the released particles of CR and ttC³ induced an acute inflammatory response and (secondary) DNA damage. Transcriptome analysis indicated that CR and ttC³ particles carried out their toxicity via different mechanisms. While ttC³ affected pro-fibrotic pathways, CR was mostly involved in DNA damage response and in pro-oncogenic signaling.
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Contaminantes Atmosféricos , Hidrocarburos Policíclicos Aromáticos , Humanos , Material Particulado/análisis , Contaminantes Atmosféricos/análisis , Tamaño de la Partícula , Pulmón , Células Epiteliales , Hidrocarburos Policíclicos Aromáticos/análisis , Inflamación/metabolismo , Daño del ADN , Materiales de Construcción , FibroblastosRESUMEN
Superparamagnetic iron oxide nanoparticles (SPIONs) have gained increasing interest in nanomedicine, but most of those that have entered the clinical trials have been withdrawn due to toxicity concerns. Therefore, there is an urgent need to design low-risk and biocompatible SPION formulations. In this work, we present an original safe-by-design nanoplatform made of silica nanoparticles loaded with SPIONs and decorated with polydopamine (SPIONs@SiO2-PDA) and the study of its biocompatibility performance by an ad hoc thorough in vitro to in vivo nanotoxicological methodology. The results indicate that the SPIONs@SiO2-PDA have excellent colloidal stability in serum-supplemented culture media, even after long-term (24 h) exposure, showing no cytotoxic or genotoxic effects in vitro and ex vivo. Physiological responses, evaluated in vivo using Caenorhabditis elegans as the animal model, showed no impact on fertility and embryonic viability, induction of an oxidative stress response, and a mild impact on animal locomotion. These tests indicate that the synergistic combination of the silica matrix and PDA coating we developed effectively protects the SPIONs, providing enhanced colloidal stability and excellent biocompatibility.
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Nanopartículas de Magnetita , Animales , Nanopartículas de Magnetita/toxicidad , Dióxido de Silicio/farmacología , Nanopartículas Magnéticas de Óxido de Hierro , Indoles/farmacologíaRESUMEN
BACKGROUND: Secondary organic aerosols (SOAs) formed from anthropogenic or biogenic gaseous precursors in the atmosphere substantially contribute to the ambient fine particulate matter [PM ≤2.5µm in aerodynamic diameter (PM2.5)] burden, which has been associated with adverse human health effects. However, there is only limited evidence on their differential toxicological impact. OBJECTIVES: We aimed to discriminate toxicological effects of aerosols generated by atmospheric aging on combustion soot particles (SPs) of gaseous biogenic (ß-pinene) or anthropogenic (naphthalene) precursors in two different lung cell models exposed at the air-liquid interface (ALI). METHODS: Mono- or cocultures of lung epithelial cells (A549) and endothelial cells (EA.hy926) were exposed at the ALI for 4 h to different aerosol concentrations of a photochemically aged mixture of primary combustion SP and ß-pinene (SOAßPIN-SP) or naphthalene (SOANAP-SP). The internally mixed soot/SOA particles were comprehensively characterized in terms of their physical and chemical properties. We conducted toxicity tests to determine cytotoxicity, intracellular oxidative stress, primary and secondary genotoxicity, as well as inflammatory and angiogenic effects. RESULTS: We observed considerable toxicity-related outcomes in cells treated with either SOA type. Greater adverse effects were measured for SOANAP-SP compared with SOAßPIN-SP in both cell models, whereas the nano-sized soot cores alone showed only minor effects. At the functional level, we found that SOANAP-SP augmented the secretion of malondialdehyde and interleukin-8 and may have induced the activation of endothelial cells in the coculture system. This activation was confirmed by comet assay, suggesting secondary genotoxicity and greater angiogenic potential. Chemical characterization of PM revealed distinct qualitative differences in the composition of the two secondary aerosol types. DISCUSSION: In this study using A549 and EA.hy926 cells exposed at ALI, SOA compounds had greater toxicity than primary SPs. Photochemical aging of naphthalene was associated with the formation of more oxidized, more aromatic SOAs with a higher oxidative potential and toxicity compared with ß-pinene. Thus, we conclude that the influence of atmospheric chemistry on the chemical PM composition plays a crucial role for the adverse health outcome of emissions. https://doi.org/10.1289/EHP9413.
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Contaminantes Atmosféricos , Hollín , Aerosoles/análisis , Anciano , Envejecimiento , Contaminantes Atmosféricos/análisis , Contaminantes Atmosféricos/toxicidad , Células Endoteliales/química , Células Endoteliales/metabolismo , Humanos , Pulmón/metabolismo , Material Particulado/análisisRESUMEN
The health effects of exposure to secondary organic aerosols (SOAs) are still limited. Here, we investigated and compared the toxicities of soot particles (SP) coated with ß-pinene SOA (SOAßPin-SP) and SP coated with naphthalene SOA (SOANap-SP) in a human bronchial epithelial cell line (BEAS-2B) residing at the air-liquid interface. SOAßPin-SP mostly contained oxygenated aliphatic compounds from ß-pinene photooxidation, whereas SOANap-SP contained a significant fraction of oxygenated aromatic products under similar conditions. Following exposure, genome-wide transcriptome responses showed an Nrf2 oxidative stress response, particularly for SOANap-SP. Other signaling pathways, such as redox signaling, inflammatory signaling, and the involvement of matrix metalloproteinase, were identified to have a stronger impact following exposure to SOANap-SP. SOANap-SP also induced a stronger genotoxicity response than that of SOAßPin-SP. This study elucidated the mechanisms that govern SOA toxicity and showed that, compared to SOAs derived from a typical biogenic precursor, SOAs from a typical anthropogenic precursor have higher toxicological potency, which was accompanied with the activation of varied cellular mechanisms, such as aryl hydrocarbon receptor. This can be attributed to the difference in chemical composition; specifically, the aromatic compounds in the naphthalene-derived SOA had higher cytotoxic potential than that of the ß-pinene-derived SOA.