Activation-induced cell death in human peripheral blood lymphocytes after stimulation with silicate in vitro

Our plain-English summary of Activation-induced cell death in human peripheral blood lymphocytes after stimulation with silicate in vitro, by T. Aikoh, A. Tomokuni, T. Matsukii, et al (International Journal of Oncology, 1998).

The study

• Authors: T. Aikoh, A. Tomokuni, T. Matsukii, F. Hyodoh, H. Ueki, T. Otsuki, A. Ueki
• Journal: International Journal of Oncology
• Published: 1998;12(6):1355-9
• Cited by: 47 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Silica and related substances such as silicate have been proven to possess "adjuvant effects". We have previously reported a finding of polyclonal human T cell activation induced by silicate as a superantigen in vitro. In this study, we observed activation-induced cell death in human lymphocytes after stimulation with chrysotile, a kind of silicate. Apoptotic cells were detected flow cytometrically using the TUNEL assay, and the maximum appearance of TUNEL positive cells occurred on day 4 of incubation. Simultaneously the manifestation of small-sized cells in the specimens increased implying apoptosis. Fas expression on lymphocytes increased to day 3 of incubation with chrysotile, and then spontaneously decreased on day 4 when remarkable apoptosis could be detected. Based on these results it is conceivable that activation-induced cell death occurred through Fas-Fas ligand interaction in lymphocytes after stimulation with silicate in a concentration with which no acute cytotoxicity has been detected. Whether and how the repeated apoptosis in definite clones of lymphocytes causes the induction of sFas synthesis need clarification.

In plain English

This was a laboratory study of human blood cells. Blood came from healthy volunteers never exposed to silica or silicate dust; the article does not say how many. The authors grew the white blood cells for up to 6 days with or without chrysotile asbestos at 50 micrograms per millilitre, a dose their earlier work found was not directly toxic to these cells. A test for programmed cell death (apoptosis) found more dying cells with chrysotile than without. The percentage of dying cells peaked on day 4 and stayed high through day 6. The percentage of cells carrying Fas, a surface molecule involved in apoptosis, was 25% higher with chrysotile than without from day 1 to day 3. On day 4 it fell to 80% of the untreated level. After 4 days with chrysotile, no difference in dying cells was seen between separated CD4+ and CD8+ cells. The authors concluded that silicate causes stimulation-induced cell death in these lymphocytes, possibly through Fas. They said it still needs clarifying whether such repeated cell death leads to soluble Fas production.

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
• Who was studied: Peripheral blood mononuclear cells (including lymphocytes) from healthy volunteers never exposed to silica or silicate dust, at Kawasaki Medical School, Japan. The number of volunteers is not stated.
• Exposure: Chrysotile asbestos, which the authors describe as a silicate, was added to the cell cultures at 50 micrograms per millilitre for 0 to 6 days. These cells were compared with cells cultured without chrysotile. The authors describe this concentration as not acutely toxic to the cells.
• Main results:
  • Under the microscope, apoptotic cells were seen more often among cells incubated with chrysotile than among control cells.
  • The percentage of apoptotic (TUNEL positive) cells was measured from day 0 to day 6. It peaked on day 4 of incubation and remained at a high level until day 6.
  • In the Discussion, the authors wrote that the share of apoptotic (TUNEL positive) cells in this study 'seems probable' to have been at most 45% of total cells.
  • Small-sized cells, which the authors took as a sign of apoptosis, increased on day 4 in the chrysotile-treated cells. No change in cell size was seen in the control cells.
  • Monocytes (CD14+ cells) made up more than 20% of cells on day 0 and less than 2% by day 4. The authors took this to mean that the dying cells were lymphocytes, not monocytes.
  • Fas was measured as the percentage of Fas-positive cells. From day 1 to day 3, Fas expression was 25% higher in chrysotile-treated cells than in control cells. On day 4 it dropped to 80% of the control level.
  • CD4+ and CD8+ cells were separated and tested after 4 days of incubation with chrysotile. No difference in the appearance of apoptotic cells was observed between the two groups.
• The authors' conclusion: The authors concluded that silicate (tested here as chrysotile) causes stimulation-induced cell death in human peripheral blood lymphocytes, and that the Fas molecule may take part in it. They suggested that long-term exposure may cause repeated cell death in some lymphocyte clones. They said that whether and how this leads to soluble Fas production requires clarification.

Topics

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

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

Related studies

• Polyclonal human T-cell activation by silicate in vitro — A. Ueki, M. Yamaguchi, et al. (1994)
• Activation of human CD4+CD45RA+ T cells by chrysotile asbestos in vitro — K. Kinugawa, A. Ueki, et al. (1992)
• Cytotoxic and genotoxic effects of calcium silicates on human lymphocytes in vitro — M. Aslam, N. Fatima, et al. (1993)
• Reduction of chrysotile asbestos-induced genotoxicity in human peripheral blood lymphocytes by garlic extract — K. Bhattacharya, S. Yadava, et al. (2004)
• Man-made mineral fibers induce apoptosis of human peripheral blood mononuclear cells similarly to chrysotile B — Z. Ma, T. Otsuki, et al. (1999)
• Sequential immunological studies on an asbestos-exposed population. I. Factors affecting peripheral blood leucocytes and T lymphocytes — M.M. Wagner, M.J. Campbell, et al. (1979)

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