Induction of CD69 antigen expression in peripheral blood mononuclear cells on exposure to silica, but not by asbestos/chrysotile-A

Our plain-English summary of Induction of CD69 antigen expression in peripheral blood mononuclear cells on exposure to silica, but not by asbestos/chrysotile-A, by P. Wu, F. Hyodoh, T. Hatayama, et al (Immunology Letters, 2005).

The study

• Authors: P. Wu, F. Hyodoh, T. Hatayama, H. Sakaguchi, S. Hatada, Y. Miura, A. Takata-Tomokuni, H. Katsuyama, T. Otsuki
• Journal: Immunology Letters
• Published: 2005;98(1):145-52
• Cited by: 23 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

While cases of silicosis are often complicated by various autoimmune disorders, patients with asbestosis develop malignant tumors such as lung cancer and malignant mesothelioma. These differences may derive from different biological effects, particularly on immunological cells, of silica and asbestos. To find differences between silica and asbestos, the early activation antigen, CD69, on T cells was examined because dysregulated and continuous activation of T cells may promote the survival of self-recognizing T cells. After cultivation of peripheral blood mononuclear cells with or without silica or chrysotile-A, an asbestos, only silica induced CD69 expression on the lymphocytes. This induction of CD69 expression was mediated by protein kinase C activation. In addition, cell-cell contact mediated by HLA-DR was more important than soluble factors secreted from silica-phagocytosed cells such as IL-1beta, IL-6, and IL-8, even though IL-6 and IL-8 were produced during the culture of PBMCs with silica and chrysotile-A. It should be examined how these activated, CD69-expressing lymphocytes affect other immune systems as well as alter themselves in terms of cytokine production and cell-cell interaction, leading to autoimmune disorders in silicosis patients.

In plain English

This was a laboratory experiment on blood cells, not a study of people. The authors took white blood cells (peripheral blood mononuclear cells) from 10 healthy volunteers and grew them for up to 10 days with silica at two concentrations, with a standard chrysotile-A asbestos sample, with a known immune stimulant (PHA), or with nothing added. They measured CD69, a marker that appears on lymphocytes when activated. Silica significantly increased CD69 on lymphocytes, gradually from days 5 to 10. Chrysotile-A induced no CD69 at all. The silica effect was slower and weaker than the PHA effect. Silica and chrysotile-A both raised two signalling proteins, IL-6 and IL-8, and silica produced much higher levels. A protein kinase C blocker cut the fluorescence intensity of CD69 in silica-exposed cells by about 80%. Blocking the molecule HLA-DR reduced that same measure by more than 50%. The authors concluded that silica, but not chrysotile-A (the only asbestos tested), induced CD69, mainly through direct cell-to-cell contact. They suggested further study of how this may lead to autoimmune disorders in silicosis patients.

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 cultured human blood cells
• Who was studied: Peripheral blood mononuclear cells from 10 healthy volunteers who, according to the authors, had never been exposed to silica or asbestos and had no symptoms of autoimmune disease
• Exposure: Min-U-silica at 25 and 50 (units printed as 'g/ml'). UICC standard chrysotile-A asbestos at 50 (same units). PHA (0.001%) as a comparison stimulant. Cells were cultured for 1 to 10 days. Chrysotile-A was the only type of asbestos tested.
• Main results:
  • Silica at both concentrations caused a significant increase in CD69 expression on lymphocytes. Chrysotile-A at 50 did not.
  • Chrysotile-A induced no CD69 expression at all.
  • In silica-exposed cells, the mean fluorescence intensity of CD69 was between 30 and 60. In PHA-stimulated cells it was more than 100, and the PHA response appeared quickly.
  • On Western blotting, the increase in CD69 in silica-exposed cells was not remarkable.
  • Lymphocytes in direct contact with silica-ingesting cells showed stronger CD69 expression than lymphocytes separated from those cells by a membrane that let only soluble factors through.
  • Of the cytokines measured, only IL-6 and IL-8 were detectable. Both rose with silica and with chrysotile-A, and silica produced much higher levels.
  • The protein kinase C inhibitor H-7 inhibited about 80% of the mean fluorescence intensity of CD69 in silica-exposed cells. The control agent H1004 had almost no effect.
  • Neutralizing HLA-DR inhibited the mean fluorescence intensity of CD69 by more than 50%. Neutralizing IL-1, M-CSF and IL-8 inhibited it by between 10 and 20%.
• The authors' conclusion: The authors concluded that silica, but not asbestos, induced CD69 expression in lymphocytes. Chrysotile-A was the only asbestos they tested. They considered the effect mainly mediated by cell-to-cell contact (HLA-DR) and by protein kinase C. They suggested it may contribute to dysregulation of autoimmunity in silicosis patients, which needs further examination.

Topics

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

Medical terms in this study, explained in our Lexicon: Chrysotile, Silicosis, Lung Cancer, Malignant Mesothelioma, Cytokine.

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