Mineral particles of varying composition induce differential chemokine release from epithelial lung cells: importance of physico-chemical characteristics

Our plain-English summary of Mineral particles of varying composition induce differential chemokine release from epithelial lung cells: importance of physico-chemical characteristics, by J. Ovrevik, T. Myran, M. Refsnes, et al (The Annals of Occupational Hygiene, 2005).

The study

• Authors: J. Ovrevik, T. Myran, M. Refsnes, M. Låg, R. Becher, R.B. Hetland, P.E. Schwarze
• Journal: The Annals of Occupational Hygiene
• Published: 2005;49(3):219-31
• Cited by: 43 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Presently, little is known about the potential health effects of mineral particles other than asbestos and quartz. In this study, a human epithelial lung cell line (A549), primary human small airway epithelial cells (SAECs) and primary rat type 2 (T2) cells were exposed to stone quarry particles of two size fractions (<10 and <2.5 microm) from nine different rock samples. The ability to induce the release of chemokines from lung cells was investigated and compared with the particles' mineral and element composition and the amount of soluble elements. The stone particles induced the release of only low levels of interleukin (IL)-8 from A549 cells. In contrast, some of the other particles induced the release of high levels of macrophage inflammatory protein (MIP)-2 from T2 cells, and high levels of IL-8 from SAECs. Differences in particle surface area could account for differences in activity between the <10 and <2.5 microm fractions of six out of the nine rock samples. For two samples the <2.5 microm fraction was most active and for one sample the <10 microm fraction was most active. Content of the mineral plagioclase displayed a strong, negative correlation with the potential to induce MIP-2, whereas the mineral pyroxene was positively correlated with MIP-2 induction. However, neither plagioclase nor pyroxene content was sufficient to explain differences in bioactivity between the particles. No statistically significant correlation was found between the amounts of total or soluble elements and MIP-2 release. In conclusion, the results suggest that mineral particles with a high content of plagioclase have a low potential to induce a pro-inflammatory response. However, a particular mineral or element responsible for eliciting strong increases in chemokine release could not be identified. Thus, at present it appears that analysing mineral and element content is insufficient to predict stone particle bioactivity, and that biological testing is a necessity.

In plain English

This laboratory study tested whether dust from crushed stone could make lung cells grown in dishes release chemical signals of inflammation (chemokines). Asbestos was not tested. A quartz dust was the comparison particle. Rock from nine samples, taken from eight Norwegian stone quarries, was crushed into two size fractions: smaller than 10 and smaller than 2.5 micrometres. Human A549 lung cells, human small airway cells and rat lung type 2 cells were exposed for 24 hours. In A549 cells, all stone particles caused only a low increase in the signal IL-8 compared with quartz. In the rat cells, the ability to trigger the signal MIP-2 varied 20-fold between particles, and some particles produced high levels compared with quartz. Particles with more plagioclase triggered less MIP-2. Pyroxene showed a weaker positive link of borderline significance. Soluble elements showed no statistically significant link. The authors concluded that stone particles high in plagioclase appear to have a low potential to cause an inflammatory response. They also concluded that mineral and element analysis alone cannot predict this activity and that biological testing is needed.

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: Laboratory (in vitro) experiment exposing cultured lung cells to stone quarry particles and to a quartz reference particle
• Who was studied: Human alveolar epithelial cell line A549, primary human small airway epithelial cells (SAECs), and primary type 2 (T2) cells isolated from the lungs of six male Wistar Kyoto rats aged 6 to 8 weeks
• Exposure: Particles from nine rock species from eight Norwegian stone quarries, crushed and sieved into fractions smaller than 10 micrometres and smaller than 2.5 micrometres. A commercial crystalline silica (quartz, MIN-U-SIL 5) was the reference particle. No asbestos was tested.
• Main results:
  • In A549 cells, all stone particles caused only a low increase in IL-8 release compared with the quartz reference particle.
  • In rat T2 cells, particles VI10, VIII10 and IX10 (smaller than 10 micrometres) induced high levels of MIP-2 compared with quartz. In the smaller-than-2.5-micrometre fraction, particles V2.5 to VIII2.5 induced considerable increases.
  • The ability to induce MIP-2 from T2 cells varied by a factor of 20 between the least and most potent particles.
  • The stone particles fell into two groups: very active (slope 0.13 to 0.20) or producing little effect (slope 0.01 to 0.05).
  • In human small airway cells, the order of ability to induce IL-8 was particle VIII, then quartz, then particle I, in both size fractions.
  • When dose was expressed as particle surface area, the two size fractions did not differ in activity for six of the nine rock samples (I to IV, VI and VIII).
  • Plagioclase content showed a relatively strong, significant, negative correlation with the particles' ability to induce MIP-2.
  • Pyroxene content showed a weaker positive correlation with MIP-2-inducing ability, of borderline significance.
  • No statistically significant correlation was found between soluble (leached) elements and MIP-2-inducing ability.
  • Soluble arsenic correlated relatively strongly with MIP-2-inducing ability (r = 0.93, P = 0.0022). This was close to, but not below, the study's significance threshold of 0.0015.
• The authors' conclusion: The authors concluded that stone particles with a high plagioclase content appear to have a low potential to induce a pro-inflammatory response. They also concluded that no particular mineral or element could be identified as responsible for strong chemokine release, that mineral and element analysis alone is insufficient to predict stone particle bioactivity, and that biological testing is a necessity.
• Limitations the authors state:
  • Bioactivity was measured as the slope of a straight line fitted to concentration-effect data, which the authors say is not ideal because such curves are seldom linear.
  • Only one chemokine at one time point was measured, so the particles might rank differently for other chemokines or other time points.
  • The element analysis measured total particle content, which may not reflect the elements available on the particle surface.
  • There was not enough of particle IX2.5 to analyse its mineral and metal content.
  • The A549 IL-8 results varied too little to be well suited to correlation analysis.

Topics

Medical terms in this study, explained in our Lexicon: A549 Cells, Macrophage, Pyroxene.

Related studies

• Mechanisms of silica-induced IL-8 release from A549 cells: initial kinase-activation does not require EGFR activation or particle uptake — J. Øvrevik, M. Refsnes, et al. (2006)
• Mineral dusts directly induce epithelial and interstitial fibrogenic mediators and matrix components in the airway wall — J. Dai, B. Gilks, et al. (1998)
• Surface physico-chemical studies of chrysotile asbestos and related minerals — C. Jolicoeur, D. Poisson (1987)
• Crocidolite activates NF-kappa B and MIP-2 gene expression in rat alveolar epithelial cells. Role of mitochondrial-derived oxidants — K.E. Driscoll, J.M. Carter, et al. (1998)
• Ozone enhances the uptake of mineral particles by tracheobronchial epithelial cells in organ culture — A. Churg, M. Brauer, et al. (1996)
• Differential responses of murine alveolar macrophages to elongate mineral particles of asbestiform and non-asbestiform varieties: Cytotoxicity, cytokine secretion and transcriptional changes — T.O. Khaliullin, E.R. Kisin, et al. (2020)

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