The importance of mineralogical composition for the cytotoxic and pro-inflammatory effects of mineral dust

Our plain-English summary of The importance of mineralogical composition for the cytotoxic and pro-inflammatory effects of mineral dust, by V.S. Grytting, M. Refsnes, M. Låg, et al (Particle and Fibre Toxicology, 2022).

The study

• Authors: V.S. Grytting, M. Refsnes, M. Låg, E. Erichsen, T.S. Røhr, B. Snilsberg, R.A. White, J. Øvrevik
• Journal: Particle and Fibre Toxicology
• Published: 2022;19(1):46
• Cited by: 14 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Respirable mineral particles represent a potential health hazard in occupational settings and ambient air. Previous studies show that mineral particles may induce cytotoxicity and inflammatory reactions in vitro and in vivo and that the potency varies between samples of different composition. However, the reason for these differences is largely unknown and the impact of mineralogical composition on the biological effects of mineral dust remains to be determined.

Methods: We have assessed the cytotoxic and pro-inflammatory effects of ten mineral particle samples of different composition in human bronchial epithelial cells (HBEC3-KT) and THP-1-derived macrophages, as well as their membranolytic properties in erythrocytes. Moreover, the results were compiled with the results of recently published experiments on the effects of stone particle exposure and analysed using linear regression models to elucidate which mineral components contribute most to the toxicity of mineral dust.

Results: While all mineral particle samples were more cytotoxic to HBEC3-KT cells than THP-1 macrophages, biotite and quartz were among the most cytotoxic in both cell models. In HBEC3-KT cells, biotite and quartz also appeared to be the most potent inducers of pro-inflammatory cytokines, while the quartz, Ca-feldspar, Na-feldspar and biotite samples were the most potent in THP-1 macrophages. All particle samples except quartz induced low levels of membranolysis. The regression analyses revealed associations between particle bioactivity and the content of quartz, muscovite, plagioclase, biotite, anorthite, albite, microcline, calcite, chlorite, orthopyroxene, actinolite and epidote, depending on the cell model and endpoint. However, muscovite was the only mineral consistently associated with increased cytotoxicity and cytokine release in both cell models.

Conclusions: The present study provides further evidence that mineral particles may induce cytotoxicity and inflammation in cells of the human airways and that particle samples of different mineralogical composition differ in potency. The results show that quartz, while being among the most potent samples, does not fully predict the toxicity of mineral dust, highlighting the importance of other particle constituents. Moreover, the results indicate that the phyllosilicates muscovite and biotite may be more potent than other minerals assessed in the study, suggesting that this group of sheet-like minerals may warrant further attention.

© 2022. The Author(s).

In plain English

This laboratory study tested ten minerals on human cells: quartz, three feldspars, hornblende and actinolite (amphiboles), augite, orthopyroxene, biotite (a mica) and epidote. None was identified as asbestos, and the article does not describe the actinolite's form. Samples were prepared as particles under 10 µm. By volume, over 95% met this in every sample except biotite, where approximately 15% was over 10 µm. Bronchial epithelial cells and THP-1 macrophages were exposed to 0 to 400 µg/mL for 24 hours. Biotite and quartz were among the most damaging; at 400 µg/mL each cut macrophage viability by approximately 30%. Quartz damaged red blood cells from three volunteers most: approximately 15% of a positive control's effect at the highest concentration. The authors combined the cell results with their earlier stone-particle study in statistical models, excluding red blood cell results. Muscovite, a mica found mainly in one earlier anorthosite sample, was the only mineral consistently associated with cell damage and inflammatory signals in both cell types. The authors concluded that minerals other than quartz can cause inflammatory responses in airway cells, and that sheet-like micas may be more hazardous. They could not measure particle surface area.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: In vitro (cell culture) experiment, with results combined with the authors' earlier published stone-particle experiments and analysed by linear regression
• Who was studied: Human bronchial epithelial cells (HBEC3-KT) and THP-1-derived macrophages in culture, plus red blood cells (erythrocytes) from 3 volunteer donors in Norway
• Exposure: Ten mineral particle samples (quartz, Na-feldspar, K-feldspar, Ca-feldspar, hornblende, actinolite, augite, orthopyroxene, biotite, epidote) at 50 to 400 µg/mL for 24 hours. The samples were prepared by separating the fraction under 10 µm. Size was measured as cumulative volume: over 95% was below 10 µm in all samples except biotite, where approximately 15% was over 10 µm. Hornblende and actinolite are described as amphibole-group minerals. No sample is identified as asbestos, and the article does not describe whether the actinolite was fibrous.
• Main results:
  • Measured by cumulative volume, over 95% of each sample was below 10 µm, except biotite, where approximately 15% was over 10 µm.
  • In HBEC3-KT bronchial cells, biotite was the most cytotoxic sample, significantly reducing viability from 100 µg/mL.
  • In THP-1 macrophages, biotite and quartz each reduced cell viability by approximately 30% at 400 µg/mL.
  • In HBEC3-KT cells, quartz induced the highest maximum levels of all measured cytokines (CXCL8, IL-1β, IL-1α). Biotite caused significant increases at the lowest concentration.
  • In THP-1 macrophages, Ca-feldspar and quartz induced the highest CXCL8 responses, followed by Na-feldspar and biotite.
  • Quartz induced the most red blood cell lysis (hemolysis), reaching approximately 15% at the highest concentration. Results were expressed as a percentage of the positive control (0.1% triton X-100).
  • Apart from a small increase with K-feldspar, the other samples caused no significant hemolysis.
  • Hemolysis was left out of the regression analyses because it was induced almost exclusively by quartz.
  • In the regression analyses, this study's samples were combined with the earlier stone samples. Muscovite was the only mineral consistently associated with increased cytotoxicity and cytokine release in both cell models. It was present mainly in the anorthosite sample from the earlier study.
  • In HBEC3-KT cells only, larger particle size correlated positively with IL-1β release (r = 0.6483, p = 0.0426) and IL-1α release (r = 0.8393, p = 0.0024).
  • Bacterial endotoxin contamination was below 1 EU/mg in all samples.
• The authors' conclusion: The authors concluded that minerals other than quartz can induce inflammatory responses in human airway cells, and that quartz content alone may not fully predict the toxicity of mineral dust. They suggested that dust high in sheet-like mica minerals may be more hazardous and warrants further attention.
• Limitations the authors state:
  • Limited sample material prevented measuring particle surface area.
  • Particle sizes differed between samples. Potency of samples with smaller particles may have been overestimated, and potency of samples with larger particles may have been underestimated.
  • Some samples may have interfered with the hemolysis assay, so hemolytic effects may have been slightly underestimated.
  • The quartz sample's effects occurred mainly at the highest concentrations, which were excluded from the cytokine calculations and regression analyses.
  • The authors did not compare differently sized samples of the same mineral, so firm conclusions about particle size cannot be drawn.

Topics

Medical terms in this study, explained in our Lexicon: Macrophage, Cytokine, Chlorite, Actinolite, Inflammation, Phyllosilicates.

Related studies

• Cytotoxic action of mineral dusts on CHV 79 cells in vitro: factors affecting toxicity — S.O. Lock, M. Chamberlain (1983)
• Mineral particles of varying composition induce differential chemokine release from epithelial lung cells: importance of physico-chemical characteristics — J. Ovrevik, T. Myran, et al. (2005)
• Lung exposure to mineral dusts enhances the capacity of lung inflammatory cells to release superoxide — A. Cantin, F. Dubois, et al. (1988)
• The effect of different mineral dusts on the mechanism of phagocytosis: a scanning electron microscope study — K. Miller, R.I. Handfield, et al. (1978)
• Cytotoxic effects of some mineral dusts on Syrian hamster peritoneal macrophages — E. Bey, J.S. Harington (1971)
• Synthetic hydrosilicate nanotubes induce low pro-inflammatory and cytotoxic responses compared to natural chrysotile in lung cell cultures — T. Skuland, T. Maslennikova, et al. (2020)

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