A study of macrophage-mediated initiation of fibrosis by asbestos and silica using a diffusion chamber technique

Our plain-English summary of A study of macrophage-mediated initiation of fibrosis by asbestos and silica using a diffusion chamber technique, by E.D. Bateman, R.J. Emerson, P.J. Cole (British Journal of Experimental Pathology, 1982).

The study

• Authors: E.D. Bateman, R.J. Emerson, P.J. Cole
• Journal: British Journal of Experimental Pathology
• Published: 1982;63(4):414-25
• Cited by: 31 articles, as counted by NIH iCite
• Read it: PubMed · Free full text

Abstract

Several cellular interactions have been identified as potentially important in fibrogenesis induced by mineral dusts. Evaluation of their relative importance in vivo remains a problem. Sealed diffusion chambers limited by Nuclepore membranes and implanted into mouse peritoneal cavities provide a means of assessing different stages of fibrogenesis by separating initiating mechanisms (dust-macrophage-lymphocyte combinations inside the chamber) from the target tissue. Fibrous reactions surrounding the chambers were quantitated by macroscopic and histological scoring, and by measurement of 14C glycine incorporated at the reaction site. Using this model the fibrogenicity of Rhodesian A chrysotile asbestos, DQ12 quartz and haematite were compared. Whereas asbestos-macrophage ratios of between 6 . 6 and 900 micrograms/10(6) mouse peritoneal macrophages (MPM) produced fibrosis, an equivalent response was obtained with 0.05 micrograms silica/10(6) MPM. Silica in amounts greater than this produced macrophage cytotoxicity without fibrogenesis. Haematite-macrophage combinations produced no significant fibrosis. It was confirmed that a direct dust-macrophage interaction forms the essential first step in fibrogenesis by both asbestos and silica and that the fibrogenicity is mediated by diffusible factor(s). Prior stimulation of host mice with Freund's complete adjuvant modified the fibrogenic response to some dust-cell combinations, suggesting an important role for host responses in determining the outcome of fibrogenic stimuli.

In plain English

This was a laboratory experiment in mice. The authors sealed mineral dust, with or without mouse macrophages (scavenger cells), in small filter-walled chambers that held cells and dust in but let dissolved substances through. They placed these in the abdomens of MF1/OLA mice and scored the fibrous tissue that formed around them, comparing Rhodesian chrysotile A asbestos, DQ12 quartz (silica) and haematite. Asbestos alone gave reactions not significantly different from negative controls; silica alone did not start fibrosis. Asbestos with macrophages, at 6.6 to 900 micrograms per million macrophages, caused significantly more fibrosis than macrophages alone; higher doses caused no more. This reaction peaked at 2 to 4 weeks, returning to control levels by 4 months. Silica with macrophages gave a similar reaction at only 0.05 micrograms per million macrophages. Larger silica amounts left fewer surviving cells and smaller reactions. Haematite caused no extra fibrosis at its single tested dose. In mice pre-treated with Freund's complete adjuvant, dust-macrophage combinations failed to stimulate fibrosis beyond the response to dust alone. The authors concluded that dust-macrophage interaction, releasing diffusible factors, is needed to start fibrosis by both minerals.

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: Animal experiment: sealed diffusion chambers containing dust and/or cells were implanted in mouse peritoneal (abdominal) cavities, and the fibrous reaction around them was scored
• Who was studied: Outbred MF1/OLA mice, with chambers containing peritoneal macrophages (or spleen cells) taken from mice of the same strain. The scoring method was checked on 32 test groups totalling 239 diffusion chambers.
• Exposure: UICC standard Rhodesian chrysotile A asbestos, Dorentrup No. 12 (DQ12) quartz, and haematite (a non-fibrogenic dust), alone or combined with mouse peritoneal macrophages at various ratios (micrograms of mineral per million macrophages). Some host mice were first stimulated with Freund's complete adjuvant.
• Main results:
  • Chambers containing chrysotile asbestos alone produced reactions not significantly different from negative controls.
  • Silica alone did not initiate fibrosis.
  • Asbestos with macrophages at 3.3 micrograms per million macrophages produced no more fibrosis than macrophages alone. Ratios from 6.6 to 900 micrograms per million macrophages produced significantly more fibrosis.
  • For asbestos, no dose-response effect was found above 6.6 micrograms per million macrophages.
  • The asbestos-plus-macrophage reaction was greatest between 2 and 4 weeks. It subsided to control levels when chambers were left in place for 4 months.
  • The asbestos reaction did not occur when spleen cell preparations with few macrophages replaced the peritoneal macrophages.
  • Silica with macrophages at 0.05 micrograms per million macrophages produced significant fibrosis of the same order as asbestos with macrophages.
  • At silica ratios of 5.5 micrograms per million macrophages and above, the reaction was smaller than with cells alone. In these higher-dose silica groups, the surviving share of macrophages was printed as "1-4%", compared with up to 26% in the equivalent asbestos experiments.
  • Haematite with macrophages, at a single ratio of 10 micrograms per million cells, produced no greater response than macrophages alone.
  • In mice pre-stimulated with Freund's complete adjuvant, asbestos or silica combined with macrophages failed to stimulate fibrosis. The responses were the same as to dust alone.
  • Chambers with dust alone or macrophages alone tended to give greater reactions in adjuvant-stimulated mice. This increase did not reach statistical significance in any single group, but it was seen in all 5 experiments involving 72 animals.
• The authors' conclusion: The authors concluded that an interaction between minerals and macrophages is necessary to start fibrosis by both silica and asbestos. They concluded that this interaction releases diffusible fibrogenic factors from the macrophages.
• Limitations the authors state:
  • The difference in fibrogenicity between asbestos and silica may be exaggerated by the limited number of cells inside the chamber.
  • The model does not allow continuous recruitment of new macrophages, as happens in tissues.
  • Haematite was tested at only one dose; higher ratios might have given different results.
  • Results from experiments done at different times were not compared with each other.
  • Cell counts underestimated the number of viable macrophages.
  • The nature of the diffusible fibrogenic factor or factors was not determined.

Topics

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

Medical terms in this study, explained in our Lexicon: Macrophage, Fibrosis, Chrysotile, Fibrogenic.

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