Manning L S, Davis M R, Robinson B W
University Department of Medicine, Queen Elizabeth II Medical Centre, Nedlands, Western Australia.
Clin Exp Immunol. 1991 Jan;83(1):85-91. doi: 10.1111/j.1365-2249.1991.tb05593.x.
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.
接触石棉与多种恶性肿瘤的发病率增加有关,包括恶性间皮瘤(MM)。本研究评估了石棉暴露与LAK细胞的体外生成及功能之间的关系,LAK细胞是一种对MM细胞具有强大裂解活性的免疫效应细胞群体。蛇纹石(温石棉)和闪石(铁石棉和青石棉)两种形式的石棉纤维均会抑制LAK细胞的生成、活力(降低5 - 11%,P < 0.02)和细胞回收率(降低13 - 15%,P < 0.02)。然而,在闪石存在的情况下生成的LAK细胞在裂解标准肿瘤细胞靶标(K562,分别为56.4%裂解率对61.5%,P > 0.5;无显著性差异;Daudi,60.5%裂解率对64.5%,P > 0.5;无显著性差异)和MM肿瘤细胞靶标(三种MM细胞系的平均值为48.3%对46.3%,P > 0.5;无显著性差异)方面与未接触石棉的细胞一样有效,而在温石棉存在的情况下生成的LAK细胞对所测试的五个肿瘤细胞靶标中的三个的功能显著降低(P < 0.03)。在石棉纤维存在的情况下,LAK细胞对所有五个肿瘤细胞靶标的功能均降低(P < 0.01),无论细胞供体是健康个体还是MM患者。NK细胞活性也受到抑制(P < 0.01)。蛇纹石形式的石棉,即温石棉,对两种效应细胞功能的抑制作用明显强于任何一种闪石(P < 0.01)。这些发现表明,石棉暴露可能会抑制免疫效应细胞机制的功能,在某些情况下还会抑制其生成,从而增加疾病和恶性肿瘤的风险。