Factors affecting the interaction of asbestos fibres with mammalian cells: a study using cells in suspension

Our plain-English summary of Factors affecting the interaction of asbestos fibres with mammalian cells: a study using cells in suspension, by R.C. Brown, E.A. Sara, J.A. Hoskins, et al (The Annals of Occupational Hygiene, 1991).

The study

• Authors: R.C. Brown, E.A. Sara, J.A. Hoskins, C.E. Evans
• Journal: The Annals of Occupational Hygiene
• Published: 1991;35(1):25-34
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

One of the earliest events in pathogenesis by mineral fibres must be an interaction between fibre and cell surfaces. Using a simple technique in which cells in suspension were incubated with fibres and adhesion monitored by separation on a density gradient it has been shown that such interactions occur through two distinct mechanisms. The first, a charge-mediated effect, occurs with positively charged fibres such as chrysotile asbestos. The second, with amphibole or glassy fibres, is mediated by fibronectin which first binds to the fibre. The bound protein then attaches to RGD receptors on the cell surface; calcium and magnesium ions are necessary for optimal adhesion. The RGD receptors bind to a tripeptide region on the protein and small peptides containing the RGD sequence block fibre-cell interaction. If the surface silanol groups on the fibre were chemically coupled to trialkylsilyl groups then interaction was slowed.

In plain English

This was a laboratory study using mammalian cell lines in suspension, not people. The authors mixed radio-labelled cells with UICC amosite, crocidolite or chrysotile asbestos, usually at 200 micrograms per millilitre. They used a density gradient to measure how many cells had stuck to fibres. Most of the work used amosite with V79-4 cells, the cell line to which attachment was greatest. Overall binding varied from about 40 to 60% between experiments. Binding was reduced in serum depleted of the blood protein fibronectin and was partly restored when fibronectin was added back. Without calcium and magnesium, binding fell. A small peptide containing the RGD sequence, the part of fibronectin that cells grip, blocked fibre binding. Chrysotile and poly-lysine-coated amosite, both positively charged, bound rapidly to some cell types: 40 to 90% of cells attached right away. Making amosite strongly water-repellent by chemical coating prevented or strongly inhibited binding. The authors suggested that fibronectin bound to fibres may subvert normal cell receptors and contribute to fibre disease, but said the details need further work. They noted that variation between serum batches complicated statistical analysis.

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 on cultured cell lines in suspension
• Who was studied: Cultured cell lines: V79-4, C3H10T1/2, P388D1 and BL9L cells, studied at the MRC Toxicology Unit, Carshalton, U.K. Most detailed work used V79-4 cells.
• Exposure: UICC amosite, crocidolite and chrysotile asbestos, usually at a final concentration of 200 micrograms per ml. Amosite was also tested in surface-modified forms: coated with poly-lysine, or derivatized with octyldimethylchlorosilane or octadecyldimethylchlorosilane.
• Main results:
  • Overall binding of cells to fibres varied from about 40 to 60% in different experiments.
  • Of the cell lines tested, attachment was greatest with V79-4 cells.
  • In serum depleted of fibronectin, amosite binding to V79-4 cells was reduced. Adding fibronectin back partially restored it.
  • Calcium and magnesium were needed for optimal binding. In Table 2, amosite binding to V79-4 cells at 75 min was 61.6% in control medium, 18.7% in medium without calcium and magnesium, and 59.0% with calcium and magnesium added.
  • The pentapeptide GRGDS, which contains the RGD sequence, blocked amosite binding to V79-4 cells.
  • Positively charged fibres (chrysotile, and poly-lysine-coated amosite) bound rapidly to some cell types: 40 to 90% of cells became bound immediately after the fibres were added.
  • Making amosite strongly hydrophobic by surface derivatization prevented or strongly inhibited binding to V79-4 cells.
• The authors' conclusion: The authors suggested that fibronectin (RGD-containing) peptides bound to fibre surfaces may subvert the normal role of cell RGD receptors and contribute to fibre pathogenesis. They said the details of this process require further elucidation.
• Limitations the authors state:
  • Variability between experiments, mostly due to differences between serum batches, complicated traditional statistical analysis.
  • Results shown are typical results from one experiment chosen from at least three repeats.
  • The fibronectin peptide experiments could not be repeated because not enough peptide was available.
  • The role of fibronectin binding in living animals is difficult to assess, because many cells make this protein.

Topics

Medical terms in this study, explained in our Lexicon: Chrysotile, Amphibole Group.

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• The influence of mineral dusts on metabolic co-operation between mammalian cells in tissue culture — M. Chamberlain (1982)

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