Asbestos fibres inhibit the in vitro activity of lymphokine-activated killer (LAK) cells from healthy individuals and patients with malignant mesothelioma.
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.
Manning
L S
LS
University Department of Medicine, Queen Elizabeth II Medical Centre, Nedlands, Western Australia.
Davis
M R
MR
Robinson
B W
BW
D001194:Asbestos / Q000633:toxicity*; D017639:Asbestos, Amosite; D017638:Asbestos, Crocidolite; D017632:Asbestos, Serpentine; D002470:Cell Survival / Q000187:drug effects; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000276:immunology; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects*; D007694:Killer Cells, Natural / Q000187:drug effects; D008297:Male; D008654:Mesothelioma / Q000276:immunology*; D014407:Tumor Cells, Cultured
D017632:Asbestos, Serpentine; D007376:Interleukin-2; D017638:Asbestos, Crocidolite; D017639:Asbestos, Amosite; D001194:Asbestos