Asbestos induces selective release of lysosomal enzymes from mononuclear phagocytes

Our plain-English summary of Asbestos induces selective release of lysosomal enzymes from mononuclear phagocytes, by P. Davies, A.C. Allison, J. Ackerman, et al (Nature, 1974).

The study

• Authors: P. Davies, A.C. Allison, J. Ackerman, A. Butterfield, S. Williams
• Journal: Nature
• Published: 1974;251(5474):423-5
• Cited by: 156 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

In plain English

This was a laboratory experiment on cells, not a study of people. The authors exposed cultured scavenger cells (mononuclear phagocytes) from the abdominal cavity of mice to UICC chrysotile asbestos at 1 to 50 µg per ml. The cells engulfed the asbestos. After 24 hours the total amount of lysosomal enzymes (digestive enzymes held inside the cell) generally did not change significantly. However, a larger share had been released into the surrounding culture fluid, starting at 1 µg per ml and rising in proportion to dose. Lactate dehydrogenase, a marker of cell death, did not rise significantly in the fluid, so the release happened without detectable cell death. At 50 µg per ml, release of one enzyme did not differ from unexposed control cultures for the first 3 hours, became significantly higher by 4.5 hours, and reached about 70% of the total by 24 hours. The authors concluded that checking whether cells survive is not enough when testing particles for toxicity. They suggested this enzyme release may be responsible for some tissue damage seen in chronic inflammation.

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 mouse cells
• Who was studied: Mononuclear phagocytes from the peritoneal (abdominal) cavity of outbred Swiss mice of either sex, grown in culture dishes. Each value was the mean of four observations.
• Exposure: UICC chrysotile A asbestos added to the cultures at 1 to 50 µg per ml, mainly for 24 hours
• Main results:
  • The cells engulfed (phagocytosed) the asbestos. At 25 to 50 µg per ml the cells tended to form clusters and some became rounded.
  • After 24 hours of exposure, total levels of lysosomal enzymes in the cultures generally showed no significant changes.
  • The share of lysosomal enzymes found in the culture medium increased significantly at concentrations as low as 1 µg per ml. The release was directly proportional to concentration up to 50 µg per ml.
  • Asbestos up to 50 µg per ml caused no significant increase in lactate dehydrogenase (a marker of cell death) in the culture medium.
  • Levels of lactate dehydrogenase inside the cells rose with dose up to 10 µg per ml asbestos and stayed at a constant raised level above that. Similar increases were seen for another non-lysosomal enzyme, leucine-2-naphthylamidase.
  • In cultures exposed to 50 µg per ml, the distribution of beta-galactosidase between cells and medium did not change compared with control cultures for the first 3 hours. A significant increase in the medium was seen by 4.5 hours.
  • In the same 50 µg per ml cultures, about 70% of total beta-galactosidase activity was in the culture medium by 24 hours.
• The authors' conclusion: The authors concluded that asbestos can release a large proportion of these cells' lysosomal enzymes without detectable cell death, so monitoring cell survival alone is insufficient when screening particles for toxicity. They suggested this selective release may be responsible for some tissue damage in chronic inflammation. They also speculated, without testing it, that another granuloma-inducing material might be injected into the chest lining of asbestos-exposed workers to possibly prevent mesothelioma and bronchogenic cancer.

Related studies

• Lysosomal enzyme secretion by macrophages during intracellular storage of particles — R.T. Dean, W. Hylton, et al. (1979)
• Spontaneous lysosomal enzyme secretion by a murine macrophage-like cell line — W. Jessup, R.T. Dean (1980)
• Enhanced lipid peroxidation and lysosomal enzyme activity in the lungs of rats with prolonged pulmonary deposition of crocidolite asbestos — J. Jajte, I. Lao, et al. (1987)
• The selective release of lysosomal acid hydrolases from mouse peritoneal macrophages by stimuli of chronic inflammation — H.U. Schorlemmer, P. Davies, et al. (1977)
• Effects of chrysotile on a lysosomal enzyme preparation and on the hydrolytic enzyme activity of cultured alveolar macrophages — R. Desai, R.J. Richards (1983)
• Human mononuclear phagocytes express the insulin-like growth factor-II/mannose-6-phosphate receptor — W.N. Rom (1991)

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