T cell alteration caused by exposure to asbestos

Megumi Maeda, Shoko Yamamoto, Tamayo Hatayama, Hidenori Matsuzaki, Suni Lee, Naoko Kumagai-Takei, Kei Yoshitome, Yasumitsu Nishimura, Yoshinobu Kimura, Takemi Otsuki

Research output: Chapter in Book/Report/Conference proceedingChapter

5 Citations (Scopus)

Abstract

A model to examine the effects of continuous exposure to asbestos on human T cells was established to interpret experimental findings for clinical utilization. Although transient exposure causes apoptosis in the human polyclonal cell line MT-2, continuous and relatively low-dose exposure resulted in resistance against asbestos-induced apoptosis with a higher production of TGF-β and IL-10 and subsequent resistance to TGF-β-induced growth inhibition and activation of STAT3 and Bcl-2. These alterations caused by continuous exposure to chrysotile asbestos were also observed in a subline exposed continuously to crocidolite and included resistance to apoptosis, changes of cytokine production, and demonstration of the importance of Bcl-2 for resistance against apoptosis. In addition, analysis of protein expression among the MT-2 original cell line, which was never exposed to asbestos, and the continuously exposed subline showed the phosphorylation of β-actin and the increasing level of cytoskeletal molecules. These findings indicate the importance of the cytoskeleton as the initial contact site between cells and asbestos fibers, particularly fibers that cannot move into the inside of cells because of their physical features. Finally, the CXCR3 chemokine receptor and related antitumor cytokine IFN-γ were assayed in these sublines continuously exposed to asbestos, as well as in vitro stimulated freshly isolated peripheral CD4 T cells derived from healthy donors and exposed to asbestos fibers. The CXCR3 expression and production capacity for IFN-γ were reduced by asbestos exposure, and these findings were also confirmed for peripheral CD4 T cells derived from patients with pleural plaque and malignant mesothelioma. The overall findings observed in continuously exposed human T cell models will contribute towards the early detection of asbestos exposure and occurrence of mesothelioma using peripheral blood and will improve the immune status (reducing antitumor immunity in asbestos-exposed patients) through the use of certain physiological substances derived from plants, foods, and microorganisms.

Original languageEnglish
Title of host publicationBiological Effects of Fibrous and Particulate Substances
PublisherSpringer Japan
Pages195-210
Number of pages16
ISBN (Print)9784431557326, 9784431557319
DOIs
Publication statusPublished - Oct 26 2015

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Keywords

  • Apoptosis
  • Asbestos
  • Continuous exposure
  • CXCR3
  • T cell
  • β-actin

ASJC Scopus subject areas

  • Medicine(all)
  • Immunology and Microbiology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Maeda, M., Yamamoto, S., Hatayama, T., Matsuzaki, H., Lee, S., Kumagai-Takei, N., Yoshitome, K., Nishimura, Y., Kimura, Y., & Otsuki, T. (2015). T cell alteration caused by exposure to asbestos. In Biological Effects of Fibrous and Particulate Substances (pp. 195-210). Springer Japan. https://doi.org/10.1007/978-4-431-55732-6_11