Asbestos fibres inhibit the in vitro activity of lymphokine-activated killer (LAK) cells from healthy individuals and patients with malignant mesothelioma

Our plain-English summary of Asbestos fibres inhibit the in vitro activity of lymphokine-activated killer (LAK) cells from healthy individuals and patients with malignant mesothelioma, by L.S. Manning, M.R. Davis, B.W. Robinson (Clinical and Experimental Immunology, 1991).

The study

• Authors: L.S. Manning, M.R. Davis, B.W. Robinson
• Journal: Clinical and Experimental Immunology
• Published: 1991;83(1):85-91
• Cited by: 19 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Asbestos exposure is associated with an increased incidence of several malignancies, including malignant mesothelioma (MM). This study evaluates the relationship between asbestos exposure and the in vitro generation and function of LAK cells, an immune effector cell population with powerful lytic activity against MM cells. Both serpentine (chrysotile) and amphibole (amosite and crocidolite) forms of asbestos fibres suppress LAK cell generation, viability (by 5-11%, P less than 0.02) and cell recovery (by 13-15%, P less than 0.02). However, the LAK cells generated in the presence of the amphiboles were as effective as unexposed cells in lysing both standard tumour cell targets (K562, 56.4% lysis versus 61.5%, respectively, P greater than 0.5; NS; Daudi, 60.5% lysis versus 64.5% P greater than 0.5; NS), and MM tumour cell targets (mean of three MM cell lines 48.3% versus 46.3%, P greater than 0.5; NS), whereas the function of LAK cells generated in the presence of chrysotile was significantly reduced against three out of the five tumour cell targets tested (P less than 0.03). In the presence of asbestos fibres, LAK cell function was reduced against all five tumour cell targets (P less than 0.01), irrespective of whether the cell donors were healthy individuals or patients with MM. NK cell activity was also suppressed (P less than 0.01). The serpentine form of asbestos, chrysotile, was significantly more suppressive of both effector cell functions than either of the amphiboles (P less than 0.01). These findings suggest that asbestos exposure may suppress the function and in some instances the generation of immune effector cell mechanisms, thereby increasing the risk of disease and malignancy.

In plain English

This Western Australian laboratory study examined how asbestos fibres affect natural killer (NK) cells and lymphokine-activated killer (LAK) cells, immune cells that, unlike NK cells, can effectively kill mesothelioma cells. Blood cells came from eight healthy laboratory workers and seven men with malignant mesothelioma. Chrysotile, amosite or crocidolite was added while LAK cells were grown or during a 4-hour killing test against five tumour cell lines, three from mesothelioma. All three fibre types reduced the viability (by 5-11%) and recovery (by 13-15%) of LAK cells grown with them. Cells grown with amosite or crocidolite killed tumour cells as well as unexposed cells. Chrysotile-grown cells were significantly weaker against three of five targets. Fibres present during the test reduced LAK and NK activity in both donor groups, chrysotile most strongly. In six individuals, interleukin-2 raised killing without asbestos but did not significantly change the extent of asbestos-induced suppression. The authors concluded that asbestos exposure may suppress immune effector cell function, and in some instances generation, thereby increasing the risk of disease and malignancy. They noted that test-tube studies may not fully mimic events in the body.

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: In vitro laboratory experiment on human blood immune cells (LAK and NK cells) exposed to asbestos fibres
• Who was studied: Blood cells (peripheral blood mononuclear cells) from eight healthy laboratory workers (four men, four women) as controls and seven men with malignant mesothelioma. The work was done at the University Department of Medicine, Queen Elizabeth II Medical Centre, Nedlands, Western Australia. Dates of sampling are not stated. The target cells were the K562 and Daudi tumour lines and three human mesothelioma cell lines (NO36, JU77, LO68).
• Exposure: UICC reference samples of amosite, chrysotile and crocidolite asbestos. Fibres were added at 100 micrograms per millilitre, either during the 3 to 7 day LAK cell generation period or at the start of the 4-hour chromium release killing assay. The authors reported that the effect was dose dependent (data not shown) but presented only results at 100 micrograms per millilitre.
• Main results:
  • In the healthy controls, all three fibre types present during LAK cell generation reduced LAK cell viability (by 5-11%, P less than 0.02) and cell recovery (by 13-15%, P less than 0.02).
  • In the healthy controls, LAK cells generated with amosite or crocidolite lysed tumour targets as well as unexposed cells did. Lysis was 56.4% versus 61.5% against K562, 60.5% versus 64.5% against Daudi, and a mean of 48.3% versus 46.3% against the three mesothelioma lines (P greater than 0.5, not significant). LAK cells generated with chrysotile were significantly less effective against three of the five targets.
  • In the healthy controls, all three fibre types added during the 4-hour assay significantly suppressed LAK cell activity against K562, Daudi and the mesothelioma targets (P less than 0.01). Chrysotile was more suppressive than amosite or crocidolite.
  • In the healthy controls, all three fibre types suppressed NK cell activity against K562 (P less than 0.01). Chrysotile lowered lysis from 48.4% without asbestos to 14.6%. Lysis was 36.7% with amosite and 35.2% with crocidolite.
  • In six individuals, adding interleukin-2 (IL-2) to assays without asbestos significantly increased both LAK and NK cell function. IL-2 slightly diminished the suppression caused by asbestos, but the extent of asbestos-induced suppression was not significantly different with or without IL-2.
  • In the seven patients with malignant mesothelioma, asbestos significantly reduced both LAK and NK cell function (P less than 0.04), with chrysotile again the most immunosuppressive. LAK cell function was lower in patients than in controls (P less than 0.01). The extent of asbestos-induced suppression did not differ between the two groups (P greater than 0.08, not significant).
• The authors' conclusion: The authors concluded that asbestos exposure may suppress the function, and in some instances the generation, of immune effector cell mechanisms, thereby increasing the risk of disease and malignancy. They also suggested that asbestos fibres in tissues such as the lung might reduce the activity of LAK cells used in IL-2/LAK cell therapy for mesothelioma patients.
• Limitations the authors state:
  • The authors noted that in vitro studies of asbestos effects on cells may not fully mimic the complex interactions occurring in the body.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma, Asbestos Exposure, Serpentine Group, Chrysotile, Amphibole Group, Amosite, Crocidolite.

Related studies

• Asbestos and cancer: human natural killer cell activity is suppressed by asbestos fibers but can be restored by recombinant interleukin-2 — B.W. Robinson (1989)
• Effects of in vitro asbestos exposure on natural killer and antibody-dependent cellular cytotoxicity — R.G. Barbers, J. Oishi (1987)
• Natural killer cell activity in asbestos workers. Interactive effects of smoking and asbestos exposure — R.D. deShazo, J. Morgan, et al. (1988)
• Human and mouse mesotheliomas exhibit elevated AKT/PKB activity, which can be targeted pharmacologically to inhibit tumor cell growth — D.A. Altomare, H. You, et al. (2005)
• Role of fibre characteristics on cytotoxicity and induction of anaphase/telophase aberrations in rat pleural mesothelial cells in vitro: correlations with in vivo animal findings — M. Yegles, X. Janson, et al. (1995)
• Cytokine and free radical responses of alveolar macrophages in vitro to asbestos fibres — L.C. Mongan, T. Jones, et al. (2000)

Browse more research in Clinical and Experimental Immunology, or return to medical research.