Biological effects of asbestos fibers on human cells in vitro--especially on lymphocytes and neutrophils

Our plain-English summary of Biological effects of asbestos fibers on human cells in vitro--especially on lymphocytes and neutrophils, by A. Ueki (Industrial Health, 2001).

The study

• Author: A. Ueki
• Journal: Industrial Health
• Published: 2001;39(2):84-93
• Type of article: Review
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Biological effects of asbestos fibers were reviewed in relation to the polyclonal activation of human lymphocytes and to the release of free radicals from human neutrophils in vitro. Chrysotile, crocidolite, and amosite asbestos activate CD4+ T lymphocytes polyclonally, followed by activation-induced cell death (a type of apoptosis). The activation is HLA class II dependent, and certain Vbeta repertoire, e.g. Vbeta 5.3, are detected among the fractionated T cells with a high Ca++ level that had been stimulated by asbestos fibers. These observations support the possibility that asbestos acts as a superantigen, and that asbestos stimulate lymphocytes repeatedly in vivo. It has been reported that asbestos-induced cytotoxicity can be suppressed by the scavengers of superoxide or hydroxyl radical. Some of these scavengers such as dimethylsulfoxide (DMSO) or retinoic acid are known as inducers of cell differentiation. The biological functions of DMSO for cell differentiation of HL-60 cells to neutrophils are suppressed by co-culturing of crocidolite asbestos, because DMSO reacts with the hydroxyl radical released after the stimulation with crocidolite and spent itself. Superoxide dismutase (SOD) inhibited the effects of crocidolite, reacting rapidly with *O2- before the secondary release of *OH. It seems to be probable that asbestos fibers, especially crocidolite, suppress the tissue cell differentiation by releasing free radicals and by wasting inducers of cell differentiation as radical scavengers.

In plain English

This was a review of laboratory (in vitro) experiments, mostly published earlier by the author and colleagues, on how asbestos fibers affect human cells. Standard samples of chrysotile, crocidolite, amosite and anthophyllite were added to cell cultures at 50 or 100 µg/ml. Chrysotile and crocidolite increased growth of some B-lymphocyte cell lines and were toxic to fibroblast and monocytic lines. Amosite had milder effects. In human blood cells, chrysotile raised release of IL-2, a sign of lymphocyte activation, but not after cells carrying HLA class II were removed. Some samples showed increases in particular T-cell receptor types. Chrysotile-treated cells later showed more programmed cell death (apoptosis), peaking on day 4. In HL-60 cells already induced toward neutrophils with DMSO, crocidolite produced hydroxyl radical signals. Separately, asbestos, especially crocidolite, suppressed DMSO-induced maturation of HL-60 cells. The author suggested that asbestos may act as a "superantigen". The author also suggested that asbestos may hinder cell maturation by using up maturation-inducing substances that also act as radical scavengers. The asbestos experiments reviewed used cell cultures and did not test these effects in exposed people.

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: Review of laboratory (in vitro) cell-culture experiments, largely the author's group's own earlier studies
• Who was studied: Human cells in culture: several human cell lines (Raji, Daudi, SB, RPMI 1788, MOLT-4, K-562, HEL-299, J-111), peripheral blood mononuclear cells (PBMC), including lymphocytes from healthy individuals, and the HL-60 promyelocytic cell line
• Exposure: International Union against Cancer (UICC) standard reference samples of chrysotile, crocidolite, amosite and anthophyllite, added to cultures at 50 or 100 µg/ml, concentrations at which no acute cytotoxicity was detected
• Main results:
  • Human cell lines: chrysotile and crocidolite stimulated growth of the Raji, Daudi and SB B-lymphocyte cell lines and had no effect on MOLT-4, K-562 or RPMI 1788. They were significantly cytotoxic to HEL-299 fibroblasts and J-111 monocytic cells. Amosite had milder effects.
  • In PBMC stimulated with PHA, adding chrysotile made the temporary drop in the CD4 surface marker significantly larger than with PHA alone (P less than 0.01). There was no significant difference for CD8.
  • In PBMC, chrysotile, crocidolite and anthophyllite caused a significant temporary drop in CD4 within 6 to 12 hours. The drop with amosite was less prominent. CD45RA declined significantly with all four fiber types (p less than 0.05).
  • IL-2 release was significantly higher in PBMC incubated with chrysotile than in control cells (P less than 0.05). In the bioassay, mean thymidine incorporation was 10,108 d.p.m. with chrysotile versus 6424 d.p.m. for control PBMC (n=5).
  • After cells expressing HLA class II were depleted, chrysotile no longer increased IL-2 secretion. The authors interpreted this to mean that MHC class II products were needed for the T-cell response.
  • In chrysotile-stimulated lymphocytes with high calcium levels, the T-cell receptor repertoire was not restricted. Vβ 6.7 increased predominantly in one case and Vβ 5.3 in two others. This was not seen with PHA stimulation.
  • In PBMC incubated with chrysotile for 0 to 6 days, apoptotic (TUNEL-positive) cells peaked on day 4.
  • In PBMC, Fas expression with chrysotile was 25% higher than in control cells from day 1 to day 3, then fell on day 4 to 80% of the control level.
  • In HL-60 cells already induced to become neutrophils with DMSO for 10 days, crocidolite alone produced a hydroxyl radical (DMPO-OH) signal. The signal was reduced by DMSO and markedly decreased by superoxide dismutase (SOD).
  • In separate experiments, DMSO-induced differentiation of HL-60 cells was suppressed when asbestos, especially crocidolite, was added to the cultures. This effect disappeared when the cells were also cultured with SOD.
  • In HL-60 cells, more than 90% originally expressed the c-myc protein. After 4 days with DMSO, about 65% of cells were positive (P less than 0.05). When crocidolite (50 µg/ml) was added, about 88% were positive.
• The authors' conclusion: The author suggested two things. First, asbestos activates T lymphocytes as a superantigen. Second, asbestos fibers inhibit substances that induce immature cells to mature, because these substances are often radical scavengers that are used up reacting with free radicals released by asbestos.
• Limitations the authors state:
  • In related work on silica and immune disorders in silicosis patients, the author noted that patients with asbestosis had not been analysed.

Topics

Medical terms in this study, explained in our Lexicon: Chrysotile, Crocidolite, Amosite, Apoptosis, Superoxide, Hydroxyl Radical.

Related studies

• In vitro depression of human lymphocyte mitogen response (phytohaemagglutinin) by asbestos fibres — R.G. Barbers, W.W. Shih, et al. (1982)
• Activation of human CD4+CD45RA+ T cells by chrysotile asbestos in vitro — K. Kinugawa, A. Ueki, et al. (1992)
• Aryl hydrocarbon hydroxylase induction in mitogen-stimulated lymphocytes by benzanthracene or cigarette tars adsorbed to asbestos fibers — T.L. McLemore, W.T. Jenkins, et al. (1979)
• Polyclonal human T-cell activation by silicate in vitro — A. Ueki, M. Yamaguchi, et al. (1994)
• Proliferation stimulating effects of chrysotile and crocidolite asbestos fibres on B lymphocyte cell lines — A. Ueki, T. Oka, et al. (1984)
• Activation-induced cell death in human peripheral blood lymphocytes after stimulation with silicate in vitro — T. Aikoh, A. Tomokuni, et al. (1998)

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