The formation of asbestos bodies by mouse peritoneal macrophages. An in vitro study

Our plain-English summary of The formation of asbestos bodies by mouse peritoneal macrophages. An in vitro study, by H.K. Koerten, J.D. de Bruijn, W.T. Daems (The American Journal of Pathology, 1990).

The study

• Authors: H.K. Koerten, J.D. de Bruijn, W.T. Daems
• Journal: The American Journal of Pathology
• Published: 1990;137(1):121-34
• Cited by: 19 articles, as counted by NIH iCite
• Read it: PubMed · Free full text
• In J-M's library: Johns-Manville's company medical library held a copy (J-M no. 003661).

Abstract

For studies on the mechanism of asbestos body formation, Union Internationale Contre Cancer (UICC) crocidolite asbestos fibers were added to a culture of mouse peritoneal macrophages. Small asbestos fibers were totally ingested by the macrophages, but fibers too long to be taken up completely remained as a consequence extracellular. These long asbestos fibers became the basis for asbestos body formation. The basic mechanism underlying asbestos body formation was found to be the exocytotic activity of macrophages. The number of iron-rich inclusion bodies was dependent on the availability of iron in the culture media, and the same holds for the amount of iron in the asbestos body coat. This means that asbestos body formation is a phenomenon that occurs accidentally when macrophages come into contact with long fibers in an iron-rich environment. A time-dependent increase in the number, average size, and rate of segmentation of the asbestos bodies was observed. The present report is the first to describe asbestos body formation in vitro.

In plain English

This was a laboratory (in vitro) experiment. The authors took macrophages (scavenger cells) from the abdominal (peritoneal) cavity of Swiss male mice. They exposed the cells to UICC crocidolite asbestos fibers for 16 hours, then cultured them up to 12 weeks in ordinary, iron-rich or manganese-rich medium. The cells swallowed short fibers whole, but some fibers were too long. Iron-containing coats formed on these long fibers, creating asbestos bodies that appeared from 4 weeks and thickened and became more beaded. At 12 weeks the authors' table showed 69.9% of 25-to-50-micrometre fibers coated and 100% of longer fibers. Their text said almost all fibers 25 micrometres or longer were coated. Coated fibers under 25 micrometres were rare. In ordinary and manganese-rich media, only occasional very thin iron coatings appeared. Gold particles the cells took up later appeared in the coats. The authors concluded that asbestos body formation can be started in the laboratory and is at least partly due to macrophages releasing material. They proposed the cells release the contents of their lysosomes, digestive compartments, into the space between cell and fiber.

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) cell-culture experiment using light microscopy, transmission electron microscopy and X-ray microanalysis
• Who was studied: Peritoneal (abdominal cavity) macrophages collected from specific pathogen-free Swiss male mice, 6 weeks old and weighing 20 g, obtained from HARLAN CPB, Zeist, The Netherlands. The number of mice is not stated.
• Exposure: UICC crocidolite asbestos fibers at 5 micrograms per ml for 16 hours. Excess fibers were then washed off, and the cells were cultured for up to 12 weeks in one of three media: control medium, iron-rich medium (1.8 mmol/l iron as iron dextran) or manganese-rich medium (1.8 mmol/l manganese as MnCl2). Control cultures received no asbestos.
• Main results:
  • By 16 hours the macrophages had taken up most fibers, but some fibers were too long to be completely ingested by one macrophage or multinucleated cell.
  • Asbestos bodies were seen by light microscopy from 4 weeks of culture. At 4 weeks the coats were thin and segmentation was only occasional. Coat thickness increased with longer culture, and segmentation became more prominent.
  • The number of beaded (segmented) asbestos bodies increased with time.
  • Table 1: at 12 weeks, 69.9% of fibers 25 to 50 micrometres long were coated. This was up from 9.0% at 4 weeks.
  • Table 1: at 12 weeks, 100% of fibers 50 to 75 micrometres long and 100% of fibers longer than 75 micrometres were coated. These groups reached 100% from 8 weeks and 6 weeks respectively.
  • The authors' text states that almost 100% of fibers of 25 micrometres and longer had become asbestos bodies after 12 weeks. Table 1 gives 69.9% for the 25 to 50 micrometre group.
  • Coated fibers shorter than 25 micrometres were rarely observed. Table 1 shows at most 0.4% coated, at 8 weeks.
  • X-ray microanalysis showed iron, and frequently chlorine, in the asbestos body coats.
  • In iron-rich medium, macrophages formed numerous iron-containing inclusion bodies, 110.5 plus or minus 56.1 per cell section.
  • In standard medium, which was low in iron, only occasional extremely thin layers of iron-stained material were seen along fibers at 6 weeks or longer.
  • In manganese-rich medium, fiber coating remained at the level of the control cultures. Manganese was not detected in inclusion bodies or in fiber deposits.
  • Gold particles taken up by the macrophages were found in the inclusion bodies and later in the asbestos body coats.
  • A cerium signal was found in the inclusion bodies and in the asbestos body coats. Cerium was the tracer used to show the enzyme acid phosphatase.
  • Macrophages were still viable at the end of the longest interval studied (12 weeks).
• The authors' conclusion: The authors concluded that asbestos body formation by mouse peritoneal macrophages can be initiated in vitro. They also concluded that the results support their earlier assumption that asbestos body formation is at least partially the result of exocytotic activity of macrophages. In their postulated mechanism, contact with a fiber too long to ingest leads the macrophage to exocytose its lysosomal contents into the space between the fiber and the macrophage. They described the process as coincidental and dependent on the contents of the lysosomes.

Topics

Medical terms in this study, explained in our Lexicon: Asbestos Bodies, Macrophage, Asbestos Body Formation, UICC, Crocidolite.

Related studies

• Asbestos body formation and iron accumulation in mouse peritoneal granulomas after the introduction of crocidolite asbestos fibers — H.K. Koerten, J. Hazekamp, et al. (1990)
• The selective release of lysosomal acid hydrolases from mouse peritoneal macrophages by stimuli of chronic inflammation — H.U. Schorlemmer, P. Davies, et al. (1977)
• In vitro studies on the cytotoxic action of different varieties of asbestos dust on macrophages — J.L. Kaw, S.H. Zaidi (1975)
• Size-dependent superparamagnetic iron oxide nanoparticles dictate interleukin-1β release from mouse bone marrow-derived macrophages — S. Chen, S. Chen, et al. (2018)
• Production of arachidonic acid metabolites by macrophages exposed in vitro to asbestos, carbonyl iron particles, or calcium ionophore — S. Kouzan, A.R. Brody, et al. (1985)
• Production of nitric oxide elevates nitrosothiol formation resulting in decreased glutathione in macrophages exposed to asbestos or asbestos substitutes — T. Nishiike, Y. Nishimura, et al. (2005)

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