Inhibitory effects of anti-oxidants on apoptosis of a human polyclonal T-cell line, MT-2, induced by an asbestos, chrysotile-A

Our plain-English summary of Inhibitory effects of anti-oxidants on apoptosis of a human polyclonal T-cell line, MT-2, induced by an asbestos, chrysotile-A, by F. Hyodoh, A. Takata-Tomokuni, Y. Miura, et al (Scandinavian Journal of Immunology, 2005).

The study

• Authors: F. Hyodoh, A. Takata-Tomokuni, Y. Miura, H. Sakaguchi, T. Hatayama, S. Hatada, H. Katsuyama, Y. Matsuo, T. Otsuki
• Journal: Scandinavian Journal of Immunology
• Published: 2005;61(5):442-8
• Cited by: 26 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

To clarify the effects of silica and silicates on cellular features of lymphocytes, a human T-lymphotropic virus type-1-immortalized polyclonal T-cell line, MT-2, was exposed to various concentrations of chrysotile-A, an asbestos classified as silicate. MT-2 cells underwent apoptosis in a dose- and time-dependent manner. The mitochondrial apoptotic pathway was activated during chrysotile-A-induced apoptosis of MT-2 cells, because of the phosphorylation of JNK and p38, increase of BAX and release of cytochrome-c from mitochondria to cytoplasma. In addition, anti-oxidants such as hydroxyl-radical excluders and capturers of superoxide and inhibitors of superoxide production effectively reduced the size of the apoptotic fraction in MT-2 cells cultured with chrysotile-A. These results indicate that the activation of reactive oxygen species may play a central role in asbestos-induced T-cell apoptosis, and anti-oxidants may help to prevent complications of pneumoconiosis.

In plain English

This was a laboratory study of cells, not of people. Researchers in Japan exposed MT-2, a human T-cell line (a kind of white blood cell) immortalized by the HTLV-1 virus, to a standard UICC sample of chrysotile-A asbestos at 0 to 50 micrograms per millilitre for up to 4 days. Cell growth fell markedly above 10 micrograms per millilitre, and the share of cells undergoing apoptosis (programmed cell death) rose with dose. The authors reported signs that this death ran mainly through the mitochondrial pathway rather than through death receptors such as Fas. Superoxide production also rose with chrysotile dose. Several anti-oxidants, including DMSO, DU, DMTU, DMPO, TMPO and inhibitors of NADPH-oxidase and cytochrome P450, reduced the dying-cell fraction. Mannitol did not. The flow-cytometry and Western-blot results were described as representative of duplicate or triplicate experiments. The authors concluded that reactive oxygen species may play a central role in asbestos-induced T-cell death and that anti-oxidants may help prevent complications of pneumoconiosis. They cautioned that they tested only short-term, high-dose exposure and that laboratory findings may not translate directly to patients.

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
• Who was studied: MT-2, a human polyclonal CD4-positive T-cell line immortalized by human T-lymphotropic virus type-1; studied at Kawasaki Medical School, Japan. No human subjects.
• Exposure: Chrysotile-A asbestos (standard UICC sample from South Africa) at 0, 5, 10, 25 and 50 micrograms per millilitre for 1 to 4 days. The figures label the unit µg/ml; the text prints it as mg/ml.
• Main results:
  • In MT-2 cells, growth was markedly reduced at more than 10 micrograms per millilitre of chrysotile-A, and the TUNEL-positive (apoptotic) fraction increased with dose across 0, 10, 25 and 50 micrograms per millilitre.
  • Cleaved caspase 3 and 9 were detected with increasing dose, but cleaved caspase 8 was not. The Fas-stimulating antibody CH11 did not affect MT-2 growth. The authors took this to mean the death-receptor pathway was not the main route.
  • Markers of the mitochondrial pathway changed with chrysotile-A dose: BAX increased, cytochrome-c was released from mitochondria into the cytoplasm, and JNK and p38 were phosphorylated.
  • Superoxide production in MT-2 cells increased with chrysotile-A concentration after 2 days of culture.
  • In cells cultured with 50 micrograms per millilitre of chrysotile-A for 2 days, the hydroxyl-radical excluders DMSO, DU and DMTU reduced apoptosis, while mannitol did not.
  • The superoxide capturers DMPO and TMPO also reduced the apoptotic (sub-G1) fraction.
  • Inhibitors of NADPH-oxidase and cytochrome P450 were described as particularly effective at reducing the apoptotic (sub-G1) fraction.
  • The flow-cytometry and Western-blot results were described as representative of duplicate or triplicate experiments.
• The authors' conclusion: The authors concluded that activation of reactive oxygen species may play a central role in asbestos-induced T-cell apoptosis, and that anti-oxidants may help to prevent complications of pneumoconiosis.
• Limitations the authors state:
  • Only short-term, high-dose exposure was tested, not the long-term, low-dose exposure that patients experience.
  • Laboratory concentrations may differ from asbestos levels in human tissue, so the results may not translate to patients.
  • It is unclear how findings from the MT-2 cell model apply clinically; the authors say they need confirming in T cells from patients.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Chrysotile.

Medical terms in this study, explained in our Lexicon: Apoptosis, Chrysotile, Silicate, Superoxide, Reactive Oxygen Species (ROS), Pneumoconiosis.

Related studies

• Man-made mineral fibers induce apoptosis of human peripheral blood mononuclear cells similarly to chrysotile B — Z. Ma, T. Otsuki, et al. (1999)
• Resistance to asbestos-induced apoptosis with continuous exposure to crocidolite on a human T cell — M. Maeda, S. Yamamoto, et al. (2012)
• Involvement of IL-10 and Bcl-2 in resistance against an asbestos-induced apoptosis of T cells — Y. Miura, Y. Nishimura, et al. (2006)
• N-acetyl L-cysteine attenuates oxidant-mediated toxicity induced by chrysotile fibers — F. Afaq, P. Abidi, et al. (2000)
• Expression of the T cell receptor Vbeta repertoire in a human T cell resistant to asbestos-induced apoptosis and peripheral blood T cells from patients with silica and asbestos-related diseases — Y. Nishimura, Y. Miura, et al. (2006)
• Death receptor 5 and cellular FLICE-inhibitory protein regulate pemetrexed-induced apoptosis in human lung cancer cells — L. Su, G. Liu, et al. (2011)

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