Man-made mineral fibers induce apoptosis of human peripheral blood mononuclear cells similarly to chrysotile B

Our plain-English summary of Man-made mineral fibers induce apoptosis of human peripheral blood mononuclear cells similarly to chrysotile B, by Z. Ma, T. Otsuki, A. Tomokuni, et al (International Journal of Molecular Medicine, 1999).

The study

• Authors: Z. Ma, T. Otsuki, A. Tomokuni, T. Aikoh, T. Matsuki, H. Sakaguchi, Y. Isozaki, F. Hyodoh, K. Uehira, K. Isoda, A. Ueki
• Journal: International Journal of Molecular Medicine
• Published: 1999;4(6):633-7
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The aim of this study was to investigate whether man-made mineral fibers (MMMF) induce apoptosis of human peripheral blood mononuclear cells (PBMC), as we recently demonstrated for chrysotile B. In vitro cultivation of PBMC with various MMMF as well as chrysotile B clearly produced apoptotic cells. The alteration of the expression for apoptosis related genes at the mRNA level during in vitro cultures of PBMC with various MMMF revealed upregulation of Flice and Apaf-1 genes and down regulation of TNF receptor 1 and Bid genes. These results indicate that MMMF induce apoptosis of PBMC in a similar manner to chrysotile B. However, the process may be mediated not only by the Fas-related apoptotic pathway but also a mitochondrial pathway. Thus, one should be aware that respiratory and immunological abnormalities may occur in workers who are exposed to MMMFs.

In plain English

This was a laboratory study on cells in culture, not on people. White blood cells (peripheral blood mononuclear cells) were taken from healthy volunteers who had never been exposed to crystalline silica; the article does not say how many. The cells were grown with chrysotile B asbestos or with other fibers: glass wool, rock wool, refractory ceramic fibers, mullite fibers, rutile whiskers and the natural mineral wollastonite. After three days, chrysotile B caused apoptosis, a form of programmed cell death, in 23.9% of cells at 50 and 31.7% at 100 micrograms per milliliter, above the level in fiber-free cultures. At the lower dose, glass wool, rutile whiskers, mullite fibers and one refractory ceramic fiber had a similar effect; the rest also raised apoptosis above fiber-free cultures. Changes in cell-death genes suggested more than one pathway was involved. The authors concluded that these fibers appeared to induce cell death similarly to chrysotile B and that exposed workers may need monitoring for immune and respiratory problems. They noted that gene activity was measured only at the mRNA level.

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) experiment on human blood cells grown in culture with fibers
• Who was studied: Peripheral blood mononuclear cells (a type of white blood cell) from healthy volunteers who had never been exposed to crystalline silica. The number of volunteers is not stated. The work was done at Kawasaki Medical School, Japan.
• Exposure: The comparison fiber was chrysotile B asbestos. The test fibers were man-made mineral fibers used as asbestos substitutes: glass wool (GW1), rock wool (RW1), refractory ceramic fibers (RF1, RF2) and mullite fibers (RF3). A rutile whisker (TO1) and the natural fibrous mineral wollastonite (WO1) were also tested. All came from the Japan Fibrous Material Research Association. Doses were 50 and 100 micrograms per milliliter, for three to six days.
• Main results:
  • Chrysotile B, day 3: 23.9% of cells at 50 micrograms per milliliter and 31.7% at 100 micrograms per milliliter were judged to be undergoing chrysotile B-induced apoptosis. These figures are after subtracting the apoptotic fraction in control cultures without fiber.
  • Day 6: the apoptotic fraction did not differ between control cultures and chrysotile B cultures.
  • At 50 micrograms per milliliter, RF2, RF3, GW1 and TO1 induced apoptosis to an extent similar to chrysotile B. Fiber-induced apoptotic fractions were 19.8%, 14.2%, 15.5% and 15.5%, against 23.9% for chrysotile B. Values are the average of two independent experiments.
  • RF1, RW1 and WO1 also increased the apoptotic fraction compared with control cultures. At 50 micrograms per milliliter the fractions were 2.3%, 9.4% and 9.8%. At 100 micrograms per milliliter they were 14.6%, 18.9% and 20.7%.
  • In most cases, cultures with 100 micrograms per milliliter of fiber had a higher apoptotic fraction than those with 50. At 100 micrograms per milliliter, TO1 and chrysotile B both reached 31.7%.
  • Gene activity was measured in cells cultured with 50 micrograms per milliliter of chrysotile B, RF2, RF3, WO1 or TO1. Flice showed the most marked change, being upregulated.
  • Culture with chrysotile B and the other fibers did not produce marked upregulation of the Fas and Fas ligand genes.
  • Bid gene expression was reduced with all fibers studied. Apaf-1 was upregulated except in the wollastonite (WO1) culture.
  • With the man-made mineral fibers, Flice and Apaf-1 were upregulated, and TNF receptor 1 and Bid were downregulated.
• The authors' conclusion: The authors concluded that man-made mineral fibers appeared to induce cell death (apoptosis) similarly to chrysotile B. They suggested this may happen through both a Fas-related and a mitochondrial pathway. They wrote that clinical observation for immunological disorders and respiratory impairment, as made in silicosis patients, may be needed in workers exposed to these fibers.
• Limitations the authors state:
  • The study only measured changes in gene expression at the mRNA level.
  • Further experiments, such as antibody neutralization and detection of caspase cleavage, are needed to clarify which cell-death pathways are involved.

Topics

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

Medical terms in this study, explained in our Lexicon: Mineral Fiber, Apoptosis, Chrysotile.

Related studies

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• Mineral fibers induce apoptosis in Syrian hamster embryo fibroblasts — E. Dopp, B. Nebe, et al. (1995)
• 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)
• N-acetylcysteine prevents cytotoxic effects induced by man-made mineral fibers in a human bronchial epithelial cell line — M. Zhang, H. Xia, et al. (2018)
• Inhibitory effects of anti-oxidants on apoptosis of a human polyclonal T-cell line, MT-2, induced by an asbestos, chrysotile-A — F. Hyodoh, A. Takata-Tomokuni, et al. (2005)
• Chrysotile Causes Human Bronchial Epithelial Cell Apoptosis in Response to the Fas-Mediated Apoptosis Pathway — M. Zhang, J. Chen, et al. (2017)

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