Asbestos-stimulated tumour necrosis factor release from alveolar macrophages depends on fibre length and opsonization

Our plain-English summary of Asbestos-stimulated tumour necrosis factor release from alveolar macrophages depends on fibre length and opsonization, by K. Donaldson, X.Y. Li, S. Dogra, et al (The Journal of Pathology, 1992).

The study

• Authors: K. Donaldson, X.Y. Li, S. Dogra, B.G. Miller, G.M. Brown
• Journal: The Journal of Pathology
• Published: 1992;168(2):243-8
• Cited by: 49 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Fibre length has been shown to be an important factor in the ability of respirable fibres to cause lung fibrosis and cancer. We have reported that a long sample of amosite asbestos is more carcinogenic and fibrogenic than a short sample of similar diameter. These amosite asbestos samples were studied with regard to their ability to stimulate the release of the pro-inflammatory cytokine tumour necrosis factor (TNF) from rat alveolar macrophages in vitro. The long fibre sample was found to stimulate substantially greater release of the cytokine than the short sample. Furthermore, on treatment of the fibres with rat immunoglobulin G (IgG), there was an increase in the ability of both the long and the short sample to stimulate TNF secretion, although the long sample retained by far the greatest activity. Coating of the fibres with a range of other proteins had no substantial effect on their ability to stimulate TNF secretion. Quartz and titanium dioxide (TiO2) were included as control particles and the TNF-stimulating activity of quartz was notably increased by opsonization with IgG. TiO2 showed a similar low activity to that of the short fibre sample of amosite but this again could be modestly increased by opsonization with IgG. The simulation of TNF release caused by treatment with immunoglobulin-opsonized long fibre amosite could be inhibited by treatment of the macrophages with the protein kinase C-inhibitor staurosporine. The study demonstrates a fibre length-related ability to stimulate cytokine secretion by alveolar macrophages, and its enhancement by opsonization with IgG.(ABSTRACT TRUNCATED AT 250 WORDS)

In plain English

This laboratory study measured how much tumour necrosis factor (TNF), an inflammation-signalling protein, rat alveolar macrophages (lung immune cells) released when exposed to dusts. It compared long-fibre and short-fibre amosite asbestos samples of similar diameter. Among counted fibres (under 3 micrometres wide, over 5 micrometres long, over three times longer than wide), more than 40 per cent in the long sample exceeded 10 micrometres, versus very few in the short sample. Quartz and titanium dioxide served as comparison dusts. Untreated long fibres caused more TNF release than short fibres (P<0.05). Short fibres matched titanium dioxide. Coating dusts with rat immunoglobulin G (IgG), an antibody, increased TNF release for all four dusts. IgG-coated long fibres remained the most active. Coating with other proteins had no substantial effect. Staurosporine, a protein kinase C blocker, reduced the TNF released by macrophages exposed to IgG-coated long fibres by 43.8, 91.0 and 55.0 per cent in three experiments. The authors concluded that macrophage TNF stimulation is related to fibre length and is enhanced by IgG coating. They noted that some differences were not statistically significant in their small number of experiments.

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 laboratory experiment using rat alveolar macrophages
• Who was studied: Alveolar macrophages obtained by bronchoalveolar lavage from normal Wistar-derived HAN strain rats, about 12 weeks old. Each experiment was repeated at least three times. The number of rats is not stated.
• Exposure: Two amosite samples were tested. The size distribution was measured on fibres less than 3 micrometres in diameter, greater than 5 micrometres in length, and with an aspect ratio of more than 3 to 1. Among these, the long-fibre amosite (LFA) had more than 40 per cent of fibres longer than 10 micrometres and 15-20 per cent longer than 20 micrometres. The short-fibre amosite (SFA) had very few fibres longer than 10 micrometres. DQ12 standard quartz and rutile titanium dioxide were the control particles. Dusts were added at 50 per ml; the unit is printed as 'pg/ml' in the scan and is likely micrograms. Before use, the dusts were pre-incubated in phosphate-buffered saline (uncoated), bovine serum albumin, rat serum, heat-inactivated rat serum, fibronectin or rat IgG.
• Main results:
  • With uncoated particles, macrophages exposed to long-fibre amosite produced more TNF than those exposed to short-fibre amosite (P<0.05). Short-fibre amosite produced the same amount as titanium dioxide.
  • Uncoated quartz produced slightly more TNF than titanium dioxide or short-fibre amosite, but this was not statistically significant.
  • Coating with IgG significantly increased TNF release for every particle type compared with uncoated particles. The P values were less than 0.001 for quartz and long-fibre amosite, and less than 0.01 for short-fibre amosite and titanium dioxide.
  • IgG-coated long-fibre amosite had the greatest activity, significantly above IgG-coated short-fibre amosite and titanium dioxide (P<0.01). IgG-coated quartz was also above IgG-coated titanium dioxide (P<0.05). IgG-coated short-fibre amosite did not differ significantly from IgG-coated titanium dioxide.
  • Coating the fibres with the other proteins tested had no substantial effect on their ability to stimulate TNF secretion.
  • Raising the IgG coating concentration to 100 and 1000 did not greatly affect TNF release with either amosite sample. A suggested rise for short-fibre amosite was not statistically significant (P>0.1).
  • The protein kinase C inhibitor staurosporine reduced the TNF released by macrophages incubated with IgG-coated long-fibre amosite. The reductions were 43.8, 91.0 and 55.0 per cent in three successive experiments, and release was not abolished completely.
• The authors' conclusion: The authors concluded that the study demonstrates a fibre length-related ability to stimulate cytokine secretion by alveolar macrophages, and that IgG coating enhances it. They considered this likely to be relevant to the relationship between fibre length and the fibres' potential to cause lung disease.
• Limitations the authors state:
  • Some differences did not reach statistical significance in the small number of experiments carried out. These were uncoated quartz versus titanium dioxide or short fibres, and the effect of IgG concentration on short fibres.
  • The authors state that diseases as complex as fibrosis or cancer will not be explained by the production of a single factor such as TNF.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Amosite.

Medical terms in this study, explained in our Lexicon: Necrosis, Alveolar Macrophage, Fibrosis, Amosite, Carcinogenic, Fibrogenic, Cytokine, Macrophage.

Related studies

• Asbestos fibers and silica particles stimulate rat alveolar macrophages to release tumor necrosis factor. Autoregulatory role of leukotriene B4 — C.M. Dubois, E. Bissonnette, et al. (1989)
• Asbestos fibres and man made mineral fibres: induction and release of tumour necrosis factor-alpha from rat alveolar macrophages — A.G. Ljungman, M. Lindahl, et al. (1994)
• Synergistic effects of mineral fibres and cigarette smoke on the production of tumour necrosis factor by alveolar macrophages of rats — Y. Morimoto, M. Kido, et al. (1993)
• Asbestos stimulates alveolar macrophages to release a factor causing human lung fibroblasts to replicate — P. Bitterman, S. Rennard, et al. (1981)
• Response of perifused alveolar macrophages to glass fibers: effect of exposure duration and fiber length — G. Forget, M.J. Lacroix, et al. (1986)
• Phagocytosis of asbestos fibers by human pulmonary alveolar macrophages — T. McLemore, M. Corson, et al. (1979)

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