Factors secreted by peritoneal macrophages are cytotoxic for transformed rat pleural mesothelium and mesothelioma cells

Our plain-English summary of Factors secreted by peritoneal macrophages are cytotoxic for transformed rat pleural mesothelium and mesothelioma cells, by I.V. Kravchenko, V.A. Furalyov, L.N. Pylev (Teratogenesis, Carcinogenesis, and Mutagenesis, 2003).

The study

• Authors: I.V. Kravchenko, V.A. Furalyov, L.N. Pylev
• Journal: Teratogenesis, Carcinogenesis, and Mutagenesis
• Published: 2003;Suppl 1:207-14
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The report is devoted to the investigation of cytotoxic action of macrophages and asbestos on transformed mesothelium and mesothelioma cells, the characterization of its specificity, and the nature of the factors mediating it. The viability of different cells after asbestos exposure was studied in co-culture with macrophages. Mesothelioma cell lines obtained from tumors developed in vivo were the most sensitive to the cytotoxic action of macrophages and asbestos. Mesothelium cells of late passages and ras-transformed cell lines IAR2 and Rat1 were somewhat less sensitive, whereas untransformed cells of IAR2 and Rat1 lines and early passage mesothelium were low sensitive to that cytotoxic action. In experiments performed on Petri dishes with inserts that allowed treatment with asbestos of only one of two cell populations, it was shown that asbestos treatment of mesothelioma cells was necessary and sufficient for manifestation of cytotoxic effect (in the absence of macrophages asbestos caused very low cytotoxicity). The medium conditioned by macrophages was not cytototoxic by itself but it strongly enhanced cytotoxic action of asbestos on transformed mesothelium and mesothelioma cells but not on normal mesothelial cells and IAR2 and Rat1 cells (both normal and ras-transformed). The specificity of this augmenting effect for different toxicants was also investigated. It was shown that medium conditioned by macrophages enhanced cytotoxicity of hydrogen peroxide and sodium azide but not that of nonfibrous silicon dioxide, ethylmethanesulfonate, and sodium dodecylsulfate. The factor mediating this effect is thermolabile, non-dialyzable and protease-sensitive. Its m.w. is approximately 3-5 kD.

Copyright 2003 Wiley-Liss, Inc.

In plain English

This was a laboratory study of cells grown in dishes, done at the Cancer Research Center in Moscow. The authors exposed rat cells to chrysotile asbestos with rat peritoneal macrophages (immune cells) or with liquid in which macrophages had been grown. The cells were rat mesothelioma lines, rat pleural mesothelial cells at an early (untransformed) and a late (spontaneously transformed) culture stage, and untransformed and ras-transformed rat liver and embryo cell lines. Mesothelioma cells were the most sensitive to macrophages plus asbestos. Untransformed (non-cancer-like) cells were affected little. When the cells were grown on separate surfaces, killing occurred only when asbestos touched the mesothelioma cells. The macrophage liquid alone was not toxic, and asbestos alone killed about 5% of cells. Together, mesothelioma cell survival did not exceed 40%, compared with 93–97% without the liquid. The liquid also increased the toxicity of hydrogen peroxide and sodium azide, but not of non-fibrous silicon dioxide, EMS or SDS. Boiling removed the liquid's activity. The active factor's molecular weight was estimated at about 3–5 kD. The authors proposed that this factor combined with asbestos could eliminate some transformed mesothelial cells, and called for further investigation.

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 experiments
• Who was studied: Cultured cells, not people. The pleural mesothelial cells came from Wistar rats: early-passage cells (passage 6) were untransformed, and late-passage cells (passage 32) had spontaneously transformed in culture. There were four rat mesothelioma cell lines. Two came from erionite-induced rat mesotheliomas, and two from mesotheliomas in Wistar rats injected intraperitoneally with chrysotile. IAR2 cells (rat liver) and Rat1 cells (rat embryo fibroblasts) were used in untransformed and ras-transformed versions. Rat peritoneal macrophages and human blood monocytes, lymphocytes and granulocytes were used to make conditioned media. The work was done at the Cancer Research Center, Moscow. Dates are not given.
• Exposure: Chrysotile asbestos (UICC Canadian chrysotile B), applied with rat peritoneal macrophages or with medium conditioned by macrophages. For comparison, conditioned medium was also combined with hydrogen peroxide, sodium azide, non-fibrous silicon dioxide (DQ12), ethylmethanesulfonate (EMS) and sodium dodecylsulfate (SDS), each at doses killing 5–7% of mesothelioma cells.
• Main results:
  • In co-culture with macrophages and asbestos, mesothelioma cells were the most sensitive. Spontaneously transformed late-passage mesothelial cells and ras-transformed cells showed less mortality. Untransformed early-passage mesothelial cells and untransformed IAR2 and Rat1 cells had little sensitivity.
  • Macrophages without asbestos had very little effect. Mesothelioma cell viability was 60% with the maximal number of macrophages, and there was no plausible cytotoxicity at lower numbers.
  • With macrophages and mesothelioma cells on separate surfaces, cell killing was seen only when asbestos contacted the mesothelioma cells. The greatest effect occurred when both cell types and asbestos shared one surface.
  • Macrophage-conditioned medium plus asbestos was cytotoxic for mesothelioma cells and, to a lesser degree, for late-passage mesothelial cells. The medium alone was not toxic to any cell line, and asbestos alone killed about 5% of cells.
  • With conditioned medium plus asbestos, mesothelioma cell viability did not exceed 40%, versus 93–97% without conditioned medium.
  • Conditioned medium also increased the toxicity of hydrogen peroxide and sodium azide, with viability of roughly 60% and 75% respectively (printed in a damaged form). There was no increase for SDS, EMS or silicon dioxide.
  • Ten minutes of boiling completely removed the conditioned medium's activity. Dialysis depleted the factor, and pronase K reduced its activity three-fold. Gel filtration put its molecular weight at 3–5 kD (data not shown).
• The authors' conclusion: The authors proposed that a factor secreted by macrophages, which they considered probably a peptide, could eliminate some transformed mesothelial cells when combined with asbestos. They said asbestos carcinogenesis involves processes acting in opposite directions that require further investigation.

Topics

Medical terms in this study, explained in our Lexicon: Macrophage, Mesothelium, Mesothelioma, Asbestos Exposure, Mesothelial Cells.

Related studies

• Cytotoxic effects of macrophages and asbestos on transformed rat mesothelial cells — V.A. Furalev, I.V. Kravchenko, et al. (2002)
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• Protective effect of natural flavonoids on rat peritoneal macrophages injury caused by asbestos fibers — V.A. Kostyuk, A.I. Potapovich, et al. (1996)
• Characterization of activated proto-oncogenes in chemically transformed Syrian hamster embryo cells — T.M. Gilmer, L.A. Annab, et al. (1988)
• Inhibition of asbestos-induced transformation of rat pleural mesothelial cells in co-culture with rat macrophages — I.V. Kravchenko, V.A. Furalyov, et al. (2001)
• Simian virus 40 and the human mesothelium — G. Klein (2000)

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