Effects of asbestos and beryllium on release of alveolar macrophage enzymes

Our plain-English summary of Effects of asbestos and beryllium on release of alveolar macrophage enzymes, by K.Y. Kang, D. Bice, R. D'Amato, et al (Archives of Environmental Health, 1979).

The study

• Authors: K.Y. Kang, D. Bice, R. D'Amato, M. Ziskind, J. Salvaggio
• Journal: Archives of Environmental Health
• Published: 1979;34(3):133-40
• Cited by: 22 articles, as counted by NIH iCite
• Read it: PubMed · Publisher
• In J-M's library: Johns-Manville's company medical library held a copy.

Abstract

Rabbit alveolar macrophages were exposed in culture medium to asbestos, beryllium sulfate, and beryllium oxide. The specific activities of the lysosomal hydrolases, acid phosphatase beta-N-acetylglucosaminidase and beta-glucuronidase plus the glycolytic enzyme, phosphohexose isomerase were determined in the medium, whole-cell homogenates, mitochondrial fractions, and supernatant. These hydrolases increased significantly in the medium but not in the mitochondrial fraction of cells exposed to dusts. Asbestos and beryllium sulfate were highly cytotoxic for alveolar macrophages in vitro and the data suggested that these agents were not associated with an increase in enzyme synthesis but rather a direct cytotoxic effect at the macrophage membrane level. For induction of enzyme release in vitro, a higher concentration of beryllium oxide was needed when compared with asbestos and beryllium sulfate. The cytotoxicity and enzyme release induced by these agents may represent an important nonspecific mechanism by which they induce inflammation and perhaps local proliferation of fibroblasts.

In plain English

This was a laboratory study of rabbit lung cells, not of people. The authors collected alveolar macrophages (immune cells that take up dust in the lungs) by washing out the lungs of 43 rabbits. They grew the cells for 24 hours with chrysotile asbestos (5 or 50 micrograms per ml), beryllium sulfate or beryllium oxide. They then measured enzymes in the culture fluid and inside the cells. With asbestos, three lysosomal enzymes rose significantly in the culture fluid, while levels inside the cells were usually low. For two of these enzymes there was no significant rise until 4.5 hours, and levels peaked at 21 hours. After 24 hours, 41.8% of cells exposed to 50 micrograms per ml of chrysotile were alive, compared with 95 to 98.4% in unexposed cultures. Under the microscope, the asbestos-exposed cells showed clustering, cell death and broken membranes. Beryllium sulfate gave a similar pattern, and beryllium oxide needed higher concentrations. The authors concluded that these agents likely damage the cell membrane directly rather than increasing enzyme production. They added that low concentrations of beryllium sulfate may stimulate enzyme production.

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 rabbit lung cells grown in culture
• Who was studied: Alveolar macrophages collected by lung washing (bronchoalveolar lavage) from 43 white New Zealand rabbits of both sexes. The rabbits had been injected with complete Freund's adjuvant supernatant 5 days before lavage. The cell preparations were about 90% macrophages.
• Exposure: Chrysotile asbestos (UICC standard, sonicated) at 5 and 50 micrograms per ml of culture medium, for 24 hours. For comparison, beryllium sulfate (3, 10 and 30 micrograms per ml) and beryllium oxide (up to 1500 micrograms per ml) were also tested.
• Main results:
  • In cultures exposed to asbestos, three lysosomal enzymes increased significantly in the culture medium, while their specific activities in cell homogenates, mitochondrial fractions and supernatants were usually low.
  • In the culture medium of cells exposed to 50 micrograms per ml asbestos, mean specific activities were 4.7 for acid phosphatase (control 1.6), 5.6 for beta-N-acetylglucosaminidase (control 0.4) and 205.2 for beta-glucuronidase (control 12.8). Each was marked as a significant increase above control. Samples per group were five to eight. (Values read from an OCR-damaged table.)
  • Over time, cells exposed to 50 micrograms per ml chrysotile showed no significant increase in release of acid phosphatase and beta-N-acetylglucosaminidase until 4.5 hours. Maximal concentrations were reached after 21 hours, with no further increase over 26 hours.
  • Release of the non-lysosomal enzyme phosphohexose isomerase rose only slightly after 10 hours of incubation with asbestos.
  • After 24 hours, cell viability was 41.8% with 50 micrograms per ml chrysotile asbestos and 45.3% with 30 micrograms per ml beryllium sulfate, compared with 95 to 98.4% in control cultures.
  • Under light microscopy, macrophages exposed to asbestos showed frequent cell clusters with bridges between cells, plus necrosis with vacuolization and disrupted cell membranes.
  • Beryllium oxide needed a higher concentration than beryllium sulfate to release lysosomal enzymes. A rise was first seen at 150 micrograms per ml.
  • In the mitochondrial fraction, a decreasing dose-response with increasing beryllium sulfate concentration led the authors to suggest that low concentrations of beryllium sulfate may stimulate enzyme synthesis.
• The authors' conclusion: The authors concluded that asbestos and beryllium salts likely do not increase enzyme production by macrophages but instead have a direct toxic effect at the macrophage membrane. They noted an exception: low concentrations of beryllium sulfate may stimulate enzyme synthesis. They suggested this membrane toxicity and enzyme release may be a nonspecific mechanism by which these agents cause inflammation and perhaps local growth of fibroblasts.
• Limitations the authors state:
  • Phosphohexose isomerase activity was already high at the start in both exposed and unexposed cultures. The authors attributed this possibly to slightly hemolyzed serum in the culture medium.
  • The authors stated that further in vitro studies are needed to understand how these agents cause fibrosis or granuloma formation.

Topics

Medical terms in this study, explained in our Lexicon: Alveolar Macrophage, Macrophage, Inflammation, Fibroblast.

Related studies

• Spontaneous lysosomal enzyme secretion by a murine macrophage-like cell line — W. Jessup, R.T. Dean (1980)
• The selective release of lysosomal acid hydrolases from mouse peritoneal macrophages by stimuli of chronic inflammation — H.U. Schorlemmer, P. Davies, et al. (1977)
• 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)
• Alveolar macrophages from patients with asbestos exposure release increased levels of leukotriene B4 — J.G. Garcia, D.E. Griffith, et al. (1989)
• Asbestos-stimulated tumour necrosis factor release from alveolar macrophages depends on fibre length and opsonization — K. Donaldson, X.Y. Li, et al. (1992)
• Asbestos stimulates alveolar macrophages to release a factor causing human lung fibroblasts to replicate — P. Bitterman, S. Rennard, et al. (1981)

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