Effect of SiO2-liberated macrophage factor on protein synthesis in connective tissue in vitro

Our plain-English summary of Effect of SiO2-liberated macrophage factor on protein synthesis in connective tissue in vitro, by M. Aalto, H. Turakainen, E. Kulonen (Scandinavian Journal of Clinical and Laboratory Investigation, 1979).

The study

• Authors: M. Aalto, H. Turakainen, E. Kulonen
• Journal: Scandinavian Journal of Clinical and Laboratory Investigation
• Published: 1979;39(3):205-13
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

1. To elucidate the role of macrophages in fibrosis the effect of the SiO2-liberated macrophage factor was assessed on protein synthesis in granulation-tissue slices. SiO2 could be replaced by chrysotile asbestos. The active factor is found in the 45/55% sucrose interface of macrophage homogenate. 2. There is no evidence of the involvement of collagenase. 3. The SiO2 effect is not influenced by the addition of yeast RNA to the incubation medium. 4. At a small concentration of polyvinylpyridine-N-oxide (PVNO) protein synthesis in the granulation tissue slices is stimulated, but at higher concentrations PVNO prevented the liberation of the fibrogenic factor from macrophages by SiO2. 5. Phospholipase C and trypsin inhibited the effect of SiO2, which was partially abolished also by heating, and by repeated freezing and thawing. 6. The macrophage RNAse, its inhibitors and fibroblast mRNA are suggested as key factors in the development of fibrosis.

In plain English

This laboratory study from the University of Turku, Finland, used rat cells and tissue. The authors treated rat peritoneal macrophage material with quartz dust (SiO2) and, in some tests, chrysotile or crocidolite asbestos. They tested whether the released 'fibrogenic factor' changed protein and collagen production, mainly in slices of rat granulation tissue. Tested on polysomes (protein-making particles) from that tissue, quartz-released factor from a macrophage fraction (45/55% sucrose) raised protein synthesis to 157 (111-235)% of control. Chrysotile also released the factor; crocidolite was only slightly effective. Phospholipase C or trypsin abolished the quartz effect; boiling, freezing-thawing and dialysis only reduced it. Yeast RNA did not change the relative effect, and there was no evidence that silica inhibited macrophage collagenase. PVNO, an anti-silicosis agent, partly blocked release of the factor during quartz treatment; small amounts seemed to stimulate collagen synthesis in the slices, and 0.1% PVNO added after release enhanced the quartz effect. The authors suggested macrophage RNAse, its inhibitors and fibroblast mRNA as key factors in fibrosis. The biological factors studied had proved hard to purify without losing activity.

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) experiments using rat macrophage preparations, tested on rat granulation-tissue slices or on polysomes isolated from granulation tissue
• Who was studied: Peritoneal macrophages from male albino rats, plus granulation tissue from viscose cellulose sponges implanted under the skin of male albino rats and harvested after 3 weeks; Department of Medical Chemistry, University of Turku, Finland
• Exposure: Quartz (SiO2) dust at 0.1-0.5 g/l, mainly Dorentrup DQ 12 quartz under 5 micrometres; other quartz samples, crocidolite asbestos and chrysotile asbestos were tested for comparison
• Main results:
  • In the subcellular fractionation experiments, the activity of supernatants from the macrophage fractions was tested on polysomes separated from granulation tissue, not on tissue slices
  • Supernatant released by quartz treatment of the 45/55% sucrose macrophage fraction raised protein synthesis in the granulation-tissue polysome test to 157 (111-235)% of the control. The 55/65% fraction gave 101 (98-103)% of its control (three experiments).
  • Chrysotile asbestos also released the fibrogenic factor from the macrophages; crocidolite was only slightly effective
  • Pre-treating the macrophage supernatant with phospholipase C or trypsin abolished the effect of quartz
  • Boiling, freezing and thawing, and overnight dialysis reduced, but did not entirely remove, the activity of the quartz-released factor
  • There was no evidence that quartz treatment inhibits macrophage collagenase
  • Adding yeast RNA or plasma membranes to the medium did not change the relative effect of quartz pre-treatment
  • When present while whole living macrophages were treated with quartz, PVNO appeared to partly inhibit release of the fibrogenic factor
  • Tested directly on granulation-tissue slices, PVNO was non-toxic at 0.1% and below, and at small concentrations seemed to stimulate collagen synthesis
  • Adding 0.1% PVNO to the macrophage supernatant after the factor had been released enhanced rather than inhibited the quartz effect
  • The quartz-released factor had no effect on detached embryonic chick tendon cells
  • In tissue slices exposed to the quartz-treated macrophage supernatant, oxygen uptake increased by an average of 33.5% and lactate formation decreased by 32.9%
  • Actinomycin did not entirely block the quartz effect, which the authors took to mean the effect does not depend on actinomycin-sensitive steps
• The authors' conclusion: The authors suggested that macrophage RNAse, its inhibitors and fibroblast mRNA are key factors in the development of fibrosis. They believed the quartz-released factor stabilizes polysomes or mRNA in fibroblasts.
• Limitations the authors state:
  • The biological factors under study had so far been difficult to purify without losing their activity
  • A final comparison of the fibrogenic factor with macrophage RNAses and a DNA-stabilizing factor must wait for immunochemical techniques
  • The authors could not exclude that the fibrogenic factor stimulates collagen synthesis directly

Topics

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

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• 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)
• Silica and asbestos: contrasts in tissue response — A.G. Heppleston (1979)
• Relative effects of asbestos and wollastonite on alveolar macrophages — W.H. Pailes, D.J. Judy, et al. (1984)
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