Nanoscale transformations of amphiboles within human alveolar epithelial cells

Our plain-English summary of Nanoscale transformations of amphiboles within human alveolar epithelial cells, by R. Vigliaturo, M. Jamnik, G. Dražić, et al (Scientific Reports, 2022).

The study

• Authors: R. Vigliaturo, M. Jamnik, G. Dražić, M. Podobnik, M.T. Žnidarič, G.D. Ventura, G.J. Redhammer, N. Žnidaršič, S. Caserman, R. Gieré
• Journal: Scientific Reports
• Published: 2022;12(1):1782
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Amphibole asbestos is related to lung fibrosis and several types of lung tumors. The disease-triggering mechanisms still challenge our diagnostic capabilities and are still far from being fully understood. The literature focuses primarily on the role and formation of asbestos bodies in lung tissues, but there is a distinct lack of studies on amphibole particles that have been internalized by alveolar epithelial cells (AECs). These internalized particles may directly interact with the cell nucleus and the organelles, exerting a synergistic action with asbestos bodies (AB) from a different location. Here we document the near-atomic- to nano-scale transformations induced by, and taking place within, AECs of three distinct amphiboles (anthophyllite, grunerite, "amosite") with different Fe-content and morphologic features. We show that: (i) an Fe-rich layer is formed on the internalized particles, (ii) particle grain boundaries are transformed abiotically by the internal chemical environment of AECs and/or by a biologically induced mineralization mechanism, (iii) the Fe-rich material produced on the particle surface does not contain large amounts of P, in stark contrast to extracellular ABs, and (iv) the iron in the Fe-rich layer is derived from the particle itself. Internalized particles and ABs follow two distinct formation mechanisms reaching different physicochemical end-states.

© 2022. The Author(s).

In plain English

This was a laboratory experiment, not a study of people. The authors exposed human lung air-sac cells of the A549 line (alveolar epithelial cells) to three amphiboles: UICC amosite (asbestiform grunerite) and non-asbestiform anthophyllite and grunerite. The dose was 50 µg/mL for 48 hours. They recovered particles the cells had taken in and examined them by electron microscopy. The particles' inner crystal structure stayed stable, but their surfaces changed. An iron-rich layer formed on all three minerals, sometimes containing tiny iron-rich clusters and nanoparticles: clusters measured on a grunerite particle averaged 1.24 nm (46 measurements) and nanoparticles measured on an anthophyllite particle 7.44 nm (84 measurements). Anthophyllite changed most, losing magnesium, aluminium and silicon, while most amosite particles showed only limited change. No phosphates were detected, which the authors contrasted with asbestos bodies described in the literature. The authors concluded that the iron most likely came from the particles themselves, and that internalized particles and asbestos bodies form by two distinct mechanisms. The authors could not tell when each particle entered a cell or whether cells stayed active throughout.

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 the particles examined by transmission electron microscopy
• Who was studied: The human alveolar epithelial cell line A549, grown on 12-well plates; no human subjects
• Exposure: Three amphiboles: UICC amosite (asbestiform grunerite), non-asbestiform anthophyllite from Kongsberg (Norway) and non-asbestiform grunerite from Salem (India), each given at 50 µg/mL for 48 hours
• Main results:
  • The inner (bulk) structure of all three amphiboles stayed stable inside the cells for at least 48 hours
  • An iron-rich layer formed on top of the silicon-rich amorphous surface layer on particles of all three amphiboles
  • Most amosite particles showed only limited change (type 1). Grunerite particles were split equally between the limited-change and highly modified types. Anthophyllite particles were the most transformed and mostly highly modified (type 2).
  • The bulk magnesium-to-iron ratio did not change significantly in grunerite and amosite, but fell substantially in anthophyllite, mainly through loss of magnesium, aluminium and silicon
  • The iron-rich clusters averaged 1.24 nm across (46 measurements) and the iron-rich nanoparticles averaged 7.44 nm across (84 measurements)
  • The cluster sizes were measured on the iron-rich layer covering a grunerite particle, and the nanoparticle sizes on the iron-rich layer covering an anthophyllite particle
  • Across all amphiboles, the iron valence state was 2.05 in the iron-rich clusters (n = 21) and 2.36 in the surrounding iron-rich layer (n = 12), meaning the layer was more oxidized
  • At the particle surface, the iron valence state after exposure to the cells was statistically identical to, or slightly lower than, that of the starting material
  • No iron phosphates or other phosphates were detected in the modified particles, which the authors described as a difference from extracellular asbestos bodies described in the literature
  • The size distributions of the clusters and nanoparticles were consistent with non-biological and/or biologically induced mineral formation, but not with biologically controlled mineral formation
• The authors' conclusion: The authors concluded that the iron in the surface layer most likely came from the amphibole particles themselves, and that particles internalized by the cells and asbestos bodies follow two distinct formation mechanisms that reach different physical and chemical end-states
• Limitations the authors state:
  • The authors could not know when a given particle was taken into a cell, or whether the cells were active during the entire 48-hour experiment
  • The number of iron valence analyses was relatively small for each type of amphibole
  • The method of using size distributions to identify how the minerals formed had never before been applied to minerals that interacted with, or were made by, eukaryotic cells
  • The authors described their expanded model of how amphiboles change inside the cells as speculative
  • The lowering of the surface iron valence state was mostly not statistically significant

Topics

Medical terms in this study, explained in our Lexicon: Amphibole Group, Amphibole Asbestos, Fibrosis, Asbestos Bodies, Anthophyllite, Grunerite, Amosite.

Related studies

• Cyto-genotoxicity of amphibole asbestos fibers in cultured human lung epithelial cell line: role of surface iron — R.K. Srivastava, M. Lohani, et al. (2010)
• Biological effects and comparative cytotoxicity of thermal transformed asbestos-containing materials in a human alveolar epithelial cell line — F. Giantomassi, A.F. Gualtieri, et al. (2010)
• SIRT3 deficiency promotes lung fibrosis by augmenting alveolar epithelial cell mitochondrial DNA damage and apoptosis — R.P. Jablonski, S.J. Kim, et al. (2017)
• The Role of Mitochondrial DNA in Mediating Alveolar Epithelial Cell Apoptosis and Pulmonary Fibrosis — S.J. Kim, P. Cheresh, et al. (2015)
• Asbestos-induced alveolar epithelial cell apoptosis. The role of endoplasmic reticulum stress response — D.W. Kamp, G. Liu, et al. (2013)
• The c-Jun N-terminal kinase signaling pathway mediates chrysotile asbestos-induced alveolar epithelial cell apoptosis — P. Li, T. Liu, et al. (2015)

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