Asbestos-induced cellular and molecular alteration of immunocompetent cells and their relationship with chronic inflammation and carcinogenesis

Our plain-English summary of Asbestos-induced cellular and molecular alteration of immunocompetent cells and their relationship with chronic inflammation and carcinogenesis, by H. Matsuzaki, M. Maeda, S. Lee, et al (Journal of Biomedicine & Biotechnology, 2012).

The study

• Authors: H. Matsuzaki, M. Maeda, S. Lee, Y. Nishimura, N. Kumagai-Takei, H. Hayashi, S. Yamamoto, T. Hatayama, Y. Kojima, R. Tabata, T. Kishimoto, J. Hiratsuka, T. Otsuki
• Journal: Journal of Biomedicine & Biotechnology
• Published: 2012;2012:492608
• Type of article: Review
• Cited by: 66 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Asbestos causes lung fibrosis known as asbestosis as well as cancers such as malignant mesothelioma and lung cancer. Asbestos is a mineral silicate containing iron, magnesium, and calcium with a core of SiO(2). The immunological effect of silica, SiO(2), involves the dysregulation of autoimmunity because of the complications of autoimmune diseases found in silicosis. Asbestos can therefore cause alteration of immunocompetent cells to result in a decline of tumor immunity. Additionally, due to its physical characteristics, asbestos fibers remain in the lung, regional lymph nodes, and the pleural cavity, particularly at the opening sites of lymphatic vessels. Asbestos can induce chronic inflammation in these areas due to the production of reactive oxygen/nitrogen species. As a consequence, immunocompetent cells can have their cellular and molecular features altered by chronic and recurrent encounters with asbestos fibers, and there may be modification by the surrounding inflammation, all of which eventually lead to decreased tumor immunity. In this paper, the brief results of our investigation regarding reduction of tumor immunity of immunocompetent cells exposed to asbestos in vitro are discussed, as are our findings concerned with an investigation of chronic inflammation and analyses of peripheral blood samples derived from patients with pleural plaque and mesothelioma that have been exposed to asbestos.

In plain English

This is a review in which the authors summarized their own earlier laboratory and blood-sample research on how asbestos may affect immune cells. It gave no new methods or full data. In earlier work they described, a natural killer (NK) cell line and NK cells from healthy donors were exposed to chrysotile. These cells showed reduced cell-killing ability and lower levels of activating receptors. Sublines of a human T-cell line, MT-2, continuously exposed to chrysotile showed reduced CXCR3 (a chemokine receptor) and reduced interferon-gamma. CD4+ T cells from six healthy donors were exposed to 10 μg/mL chrysotile for 28 days. In these cells CXCR3 fell significantly, though the authors noted this seemed to depend on one donor; four of the six showed a decrease. CXCR3 was reduced in CD4+ T cells from patients with pleural plaque or malignant mesothelioma compared with healthy donors. The difference between the two patient groups was not statistically significant. The authors proposed that asbestos alters immune cells, leading to chronic inflammation and reduced tumor immunity. They also stated that the evidence for this whole sequence is insufficient.

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 article summarizing the authors' own previously published in vitro (cell line and cultured cell) experiments and analyses of blood samples from patients
• Who was studied: A human NK cell line and NK cells from healthy donors; a human T-cell line (MT-2) with six chrysotile-exposed sublines; CD4+ T cells from six healthy donors; and CD4+ T cells from healthy donors and from patients with pleural plaque or malignant mesothelioma in Japan (patient numbers not given in this article)
• Exposure: Chrysotile asbestos in the laboratory experiments: long-term continuous exposure of the MT-2 cell line (six sublines exposed independently), and 10 μg/mL for 28 days for healthy-donor CD4+ T cells. The patients had past asbestos exposure, with no fiber type or dose given.
• Main results:
  • In the authors' earlier work, an NK cell line and fresh NK cells from healthy donors exposed long-term to chrysotile showed reduced cytotoxicity with decreased expression of activating receptors (NKG2D and 2B4 in the cell line, NKp46 in the fresh NK cells).
  • MT-2 T-cell sublines continuously exposed to chrysotile showed reduced CXCR3 expression and reduced IFN-γ production and expression compared with the original line.
  • In the MT-2 sublines, CCR5 was not significantly reduced at the mRNA level.
  • In CD4+ T cells from six healthy donors, CXCR3 expression was significantly reduced after exposure to 10 μg/mL chrysotile for 28 days; four of the six donors showed a decrease to various degrees.
  • Healthy-donor CD4+ T cells cultured with chrysotile for 28 days also showed decreased IFN-γ expression and production.
  • CXCR3 expression was reduced in CD4+ T cells from asbestos-exposed patients (pleural plaque or malignant mesothelioma) compared with healthy donors.
  • CXCR3 on CD4+ T cells from mesothelioma patients was lower than in pleural plaque patients, but the difference was not statistically significant.
  • IFN-γ expression in stimulated CD4+ T cells was reduced only in mesothelioma patients, not in those with pleural plaque.
  • As reported previously by the authors, plasma IL-6 was significantly higher in mesothelioma patients than in healthy donors, pleural plaque patients and silicosis patients.
• The authors' conclusion: The authors proposed that chronic, recurrent encounters with asbestos fibers, together with the surrounding inflammation, alter immune cells and eventually lead to decreased tumor immunity. They suggested that studying these changes may lead to new methods for preventing mesothelioma and other asbestos-related cancers.
• Limitations the authors state:
  • The authors stated there is insufficient evidence for all of the proposed sequential changes in immune cells.
  • The significant reduction of CXCR3 in healthy-donor CD4+ T cells seemed to depend on one donor in whom expression decreased markedly.
  • Culture of the healthy-donor CD4+ T cells was limited to a period of around four weeks.

Topics

Medical terms in this study, explained in our Lexicon: Chronic Inflammation, Carcinogenesis, Fibrosis, Malignant Mesothelioma, Lung Cancer, Silicate, Silicosis, Pleural Cavity.

Related studies

• Inflammatory Alteration of Human T Cells Exposed Continuously to Asbestos — N. Kumagai-Takei, S. Yamamoto, et al. (2018)
• Resistance to asbestos-induced apoptosis with continuous exposure to crocidolite on a human T cell — M. Maeda, S. Yamamoto, et al. (2012)
• Biopersistent fiber-induced inflammation and carcinogenesis: lessons learned from asbestos toward safety of fibrous nanomaterials — H. Nagai, S. Toyokuni (2010)
• Chronic inflammation in tumor stroma is an independent predictor of prolonged survival in epithelioid malignant pleural mesothelioma patients — K. Suzuki, K. Kadota, et al. (2011)
• Chronic infections and inflammatory processes as cancer risk factors: possible role of nitric oxide in carcinogenesis — H. Ohshima, H. Bartsch (1994)
• Alteration of cytoskeletal molecules in a human T cell line caused by continuous exposure to chrysotile asbestos — M. Maeda, Y. Chen, et al. (2013)

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