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Refsnes, Magne; Hetland, Ragna Bogen; Øvrevik, Johan; Sundfør, Idunn; Schwarze, Per E.; Låg, Marit

doi:10.1186/1743-8977-3-10

Cited by 23 publications

(13 citation statements)

References 45 publications

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“…While similar trends were observed, few of the apparent differences reached statistical significance in the combined culture of HBEC3-KT cells and THP-1 macrophages, compared with the corresponding monocultures. In line with previous studies from our group, differences in surface area could not fully explain the differences between the particle samples [ 47 , 48 ], suggesting that the differences in potency were due to other parameters, such as particle composition or surface reactivity. After correcting for differences in surface area, quartzite and anorthosite were the most cytotoxic particle samples in both HBEC3-KT cells and THP-1 macrophages, surpassing the effects of the α-quartz reference sample.…”

Section: Discussionsupporting

confidence: 85%

“…The high potency of the anorthosite and hornfels samples contradicts previous studies of stone- and mineral particles indicating that particle samples with high feldspar content have low cytotoxic and pro-inflammatory activity [ 45 – 48 , 50 ]. In the present study, the anorthosite, hornfels and rhomb porphyry samples all consisted primarily of feldspar minerals, but varied considerably in potency, suggesting that the total content of feldspar minerals is a poor indicator of stone-particle toxicity.…”

Section: Discussioncontrasting

confidence: 63%

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Respirable stone particles differ in their ability to induce cytotoxicity and pro-inflammatory responses in cell models of the human airways

et al. 2021

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Background Respirable stone- and mineral particles may be a major constituent in occupational and ambient air pollution and represent a possible health hazard. However, with exception of quartz and asbestos, little is known about the toxic properties of mineral particles. In the present study, the pro-inflammatory and cytotoxic responses to six stone particle samples of different composition and with diameter below 10 μm were assessed in human bronchial epithelial cells (HBEC3-KT), THP-1 macrophages and a HBEC3-KT/THP-1 co-culture. Moreover, particle-induced lysis of human erythrocytes was assessed to determine the ability of the particles to lyse biological membranes. Finally, the role of the NLRP3 inflammasome was assessed using a NLRP3-specific inhibitor and detection of ASC oligomers and cleaved caspase-1 and IL-1β. A reference sample of pure α-quartz was included for comparison. Results Several stone particle samples induced a concentration-dependent increase in cytotoxicity and secretion of the pro-inflammatory cytokines CXCL8, IL-1α, IL-1β and TNFα. In HBEC3-KT, quartzite and anorthosite were the most cytotoxic stone particle samples and induced the highest levels of cytokines. Quartzite and anorthosite were also the most cytotoxic samples in THP-1 macrophages, while anorthosite and hornfels induced the highest cytokine responses. In comparison, few significant differences between particle samples were detected in the co-culture. Adjusting responses for differences in surface area concentrations did not fully account for the differences between particle samples. Moreover, the stone particles had low hemolytic potential, indicating that the effects were not driven by membrane lysis. Pre-incubation with a NLRP3-specific inhibitor reduced stone particle-induced cytokine responses in THP-1 macrophages, but not in HBEC3-KT cells, suggesting that the effects are mediated through different mechanisms in epithelial cells and macrophages. Particle exposure also induced an increase in ASC oligomers and cleaved caspase-1 and IL-1β in THP-1 macrophages, confirming the involvement of the NLRP3 inflammasome. Conclusions The present study indicates that stone particles induce cytotoxicity and pro-inflammatory responses in human bronchial epithelial cells and macrophages, acting through NLRP3-independent and -dependent mechanisms, respectively. Moreover, some particle samples induced cytotoxicity and cytokine release to a similar or greater extent than α-quartz. Thus, these minerals warrant further attention in future research.

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Section: Discussionsupporting

confidence: 85%

Section: Discussioncontrasting

confidence: 63%

Respirable stone particles differ in their ability to induce cytotoxicity and pro-inflammatory responses in cell models of the human airways

et al. 2021

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“…Even for a specific type of effects (i.e., inflammatory responses) the rank order of potency among different particle types may vary between different cell types and between in vitro cell culture tests and in vivo animal studies. This has been reported in a number of studies on ambient air PM as well as mineral particles and nanomaterials [105,124,125,126,127,128,129,130,131,132,133,134]. These observations not only suggest the existence of a variety of triggering mechanisms for particle toxicity and that different particle characteristics may act as critical determinants for different toxicological effects, but also that triggering mechanisms may vary between different cell types and target organs.…”

Section: Discussionsupporting

confidence: 55%

Oxidative Potential Versus Biological Effects: A Review on the Relevance of Cell-Free/Abiotic Assays as Predictors of Toxicity from Airborne Particulate Matter

Øvrevik

2019

IJMS

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Background and Objectives: The oxidative potential (OP) of particulate matter (PM) in cell-free/abiotic systems have been suggested as a possible measure of their biological reactivity and a relevant exposure metric for ambient air PM in epidemiological studies. The present review examined whether the OP of particles correlate with their biological effects, to determine the relevance of these cell-free assays as predictors of particle toxicity. Methods: PubMed, Google Scholar and Web of Science databases were searched to identify relevant studies published up to May 2019. The main inclusion criteria used for the selection of studies were that they should contain (1) multiple PM types or samples, (2) assessment of oxidative potential in cell-free systems and (3) assessment of biological effects in cells, animals or humans. Results: In total, 50 independent studies were identified assessing both OP and biological effects of ambient air PM or combustion particles such as diesel exhaust and wood smoke particles: 32 in vitro or in vivo studies exploring effects in cells or animals, and 18 clinical or epidemiological studies exploring effects in humans. Of these, 29 studies assessed the association between OP and biological effects by statistical analysis: 10 studies reported that at least one OP measure was statistically significantly associated with all endpoints examined, 12 studies reported that at least one OP measure was significantly associated with at least one effect outcome, while seven studies reported no significant correlation/association between any OP measures and any biological effects. The overall assessment revealed considerable variability in reported association between individual OP assays and specific outcomes, but evidence of positive association between intracellular ROS, oxidative damage and antioxidant response in vitro, and between OP assessed by the dithiothreitol (DDT) assay and asthma/wheeze in humans. There was little support for consistent association between OP and any other outcome assessed, either due to repeated lack of statistical association, variability in reported findings or limited numbers of available studies. Conclusions: Current assays for OP in cell-free/abiotic systems appear to have limited value in predicting PM toxicity. Clarifying the underlying causes may be important for further advancement in the field.

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“…Rat macrophages show a stronger apoptotic response to smaller silica particles than larger particles. ( 56 ) The crystalline silica particles used in the present study ranged from 2 µm to 20 µm as assessed by in-air micro-PIXE analysis, and these sizes were similar to those used in previous reports. ( 16 , 57 ) Whether p62 expression can be affected by silica particle size has not been established.…”

Section: Discussionsupporting

confidence: 82%

Co-localization of iron binding on silica with p62/sequestosome1 (SQSTM1) in lung granulomas of mice with acute silicosis

Shimizu

Dobashi

Nagase

et al. 2015

J. Clin. Biochem. Nutr.

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The cellular mechanisms involved in the development of silicosis have not been fully elucidated. This study aimed to examine influence of silica-induced lung injury on autophagy. Suspensions of crystalline silica particles were administered transnasally to C57BL/6j mice. Immunohistochemical examination for Fas and p62 protein expression was performed using lung tissue specimens. Two-dimensional and quantitative analysis of silica deposits in the lungs were performed in situ using lung tissue sections by an in-air microparticle induced X-ray emission (in-air micro-PIXE) analysis system, which was based on irrradiation of specimens with a proton ion microbeam. Quantitative analysis showed a significant increase of iron levels on silica particles (assessed as the ratio of Fe relative to Si) on day 56 compared with day 7 (p<0.05). Fas and p62 were expressed by histiocytes in granulomas on day 7, and the expressions persisted for day 56. Fas- and p62-expressing histiocytes were co-localized in granulomas with silica particles that showed an increase of iron levels on silica particles in mouse lungs. Iron complexed with silica induces apoptosis, and may lead to dysregulations of autophagy in histiocytes of granulomas, and these mechanisms may contribute to granuloma development and progression in silicosis.

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Untitled

Cited by 23 publications

References 45 publications

Respirable stone particles differ in their ability to induce cytotoxicity and pro-inflammatory responses in cell models of the human airways

Respirable stone particles differ in their ability to induce cytotoxicity and pro-inflammatory responses in cell models of the human airways

Oxidative Potential Versus Biological Effects: A Review on the Relevance of Cell-Free/Abiotic Assays as Predictors of Toxicity from Airborne Particulate Matter

Co-localization of iron binding on silica with p62/sequestosome1 (SQSTM1) in lung granulomas of mice with acute silicosis

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