Dysregulation of the immune system caused by silica and asbestos

Our plain-English summary of Dysregulation of the immune system caused by silica and asbestos, by M. Maeda, Y. Nishimura, N. Kumagai, et al (Journal of Immunotoxicology, 2010).

The study

• Authors: M. Maeda, Y. Nishimura, N. Kumagai, H. Hayashi, T. Hatayama, M. Katoh, N. Miyahara, S. Yamamoto, J. Hirastuka, T. Otsuki
• Journal: Journal of Immunotoxicology
• Published: 2010;7(4):268-78
• Type of article: Review
• Cited by: 67 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Silica and asbestos cause pneumoconioses known as silicosis and asbestosis, respectively, that are each characterized by progressive pulmonary fibrosis. While local effects of inhaled silica particles alter the function of alveolar macrophages and sequential cellular and molecular biological events, general systemic immunological effects may also evolve. One well-known health outcome associated with silica exposure/silicosis is an increase in the incidence of autoimmune disorders. In addition, while exposure to silica--in the crystalline form--has also been seen to be associated with the development of lung cancers, it remains unclear as to whether or not silicosis is a necessary condition for the elevation of silica-associated lung cancer risks. Since asbestos is a mineral silicate, it would be expected to also possess generalized immunotoxicological effects similar to those associated with silica particles. However, asbestos-exposed patients are far better known than silicotic patients for development of malignant diseases such as lung cancer and mesothelioma, and less so for the development of autoimmune disorders. With both asbestos and crystalline silica, one important dysregulatory outcome that needs to be considered is an alteration in tumor immunity that allows for silica- or asbestos- (or asbestos-associated agent)-induced tumors to survive and thrive in situ. In this review, the immunotoxicological effects of both silica and asbestos are presented and contrasted in terms of their abilities to induce immune system dysregulation that then are manifest by the onset of autoimmunity or by alterations in host-tumor immunity.

In plain English

This was a review by a research group at Kawasaki Medical School, Japan. It mainly summarized the group's own earlier studies of how silica and asbestos may disturb immunity. The silica work involved Japanese brickyard workers with silicosis and no autoimmune symptoms or cancers. Their blood showed autoantibodies, including anti-Fas, and more serum soluble Fas than healthy donors'. After age correction, their CD4+CD25+ blood-cell fraction, where regulatory T cells are found, was smaller and less suppressive. The authors noted this fraction may also include chronically activated responder T cells. The asbestos work used chrysotile. A human natural killer (NK) cell line continuously exposed to chrysotile showed fewer activating receptors, less granzyme A and lower killing activity. NK cells from mesothelioma patients showed reduced NKp46. A human T-cell line died by apoptosis after short, high-dose chrysotile exposure. After about one year of continuous exposure it became resistant to asbestos-induced apoptosis and overproduced IL-10. Cytotoxic T-cell results were called preliminary. The authors concluded it remains unclear whether asbestos alters immune function. They suggested that chronic low-dose exposure would likely reduce tumor immunity.

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 (and others') earlier laboratory and clinical investigations
• Who was studied: For silica: Japanese brickyard workers with silicosis in Bizen City, Okayama prefecture, Japan, without clinical autoimmune symptoms or cancers, compared with healthy donors (numbers not given). For asbestos: human NK and T-cell lines, NK cells from mesothelioma patients and healthy donors, and samples from patients with pleural plaque or malignant mesothelioma (numbers not given).
• Exposure: Crystalline silica in materials handled by brickyard workers, estimated at up to 40 to 60% by mass. Chrysotile asbestos applied to cell lines in laboratory experiments, both short-term high-dose and long-term continuous exposure.
• Main results:
  • Silicosis patients had autoantibodies against Fas and caspase-8, as well as topoisomerase I and desmoglein.
  • Serum soluble Fas was higher in silicosis patients than in healthy donors. Serum soluble Fas ligand did not differ between the groups.
  • After correction for donor age, the CD4+CD25+ cell fraction (in which regulatory T cells are found) was lower in silicosis patients than in healthy donors. In functional assays these CD4+CD25+ cells showed reduced suppressive effect. The authors concluded that regulatory T-cell function and numbers were likely reduced.
  • A human NK cell line continuously exposed to chrysotile (YT-CB5) showed significant reductions in the activating receptors NKG2D and 2B4 and in granzyme A. The authors reported that asbestos exposure decreased NK cell killing activity.
  • Freshly isolated NK cells from mesothelioma patients, and NK cells from healthy donors cultured with asbestos, showed reduced expression of the activating receptor NKp46.
  • Short-term (1 to 4 days), high-dose chrysotile exposure of the MT-2 human T-cell line caused apoptosis that depended on time and dose.
  • After about 1 year of continuous chrysotile exposure, the MT-2 subline became resistant to asbestos-induced apoptosis. It showed excess IL-10, Bcl-2 over-expression, excess TGF-beta, and over-expression of multiple T-cell receptor V-beta forms.
  • In clinical samples, plasma IL-10 and TGF-beta and bcl-2 gene expression in peripheral CD4+ T-lymphocytes were reported as elevated compared with healthy donors. The patient group is described inconsistently (see text problems).
• The authors' conclusion: The authors concluded that it still remains unclear whether asbestos is an immunomodulant, and whether it affects tumor immunity. They also stated that their findings indicated chronic, low-dose asbestos exposure of immune cells would likely reduce a host's tumor immunity.
• Limitations the authors state:
  • The CD4+CD25+ fraction measured in silicosis patients may include chronically activated responder T cells as well as true regulatory T cells.
  • The effects of asbestos on regulatory T-cell function and numbers have not yet been analyzed directly.
  • Results on asbestos and cytotoxic T-lymphocyte function were preliminary and awaiting peer review.
  • Changes in resistance to tumors arising naturally in the body (as opposed to implanted tumors) after silica exposure have not been evaluated to the same degree in the literature.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Silicosis, Pulmonary Fibrosis, Alveolar Macrophage, Crystalline, Lung Cancer, Silicate, Mesothelioma.

Related studies

• Silica exposure and altered regulation of autoimmunity — S. Lee, H. Matsuzaki, et al. (2014)
• Far-reaching consequences of high level air pollution on the developing immune system — T. Turnovska, I. Sirakova, et al. (2001)
• Respiratory impairments due to dust exposure: a comparative study among workers exposed to silica, asbestos, and coalmine dust — X. Wang, E. Yano, et al. (1997)
• Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica — C. Dostert, V. Pétrilli, et al. (2008)
• Immune responses in the Japanese pufferfish (Takifugu rubripes) head kidney cells stimulated with particulate silica — T. Morimoto, G. Biswas, et al. (2016)
• Functional expression of system x(c)- is upregulated by asbestos but not crystalline silica in murine macrophages — J.C. Pfau, T. Seib, et al. (2012)

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