IMPAIRMENT IN CYTOTOXICITY AND EXPRESSION OF NK CELL- ACTIVATING RECEPTORS ON HUMAN NK CELLS FOLLOWING EXPOSURE TO ASBESTOS FIBERS
IMPAIRMENT IN CYTOTOXICITY AND EXPRESSION OF NK CELL- ACTIVATING RECEPTORS ON HUMAN NK CELLS FOLLOWING EXPOSURE TO ASBESTOS FIBERS
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DOI：
10.1177/039463200902200304
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发表时间：
2009-07-01
影响因子：
3.5
通讯作者：
Otsuki, T.
中科院分区：
文献类型：
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作者：
Nishimura, Y.;Miura, Y.;Otsuki, T.
天冬氨酸以其致瘤活性而闻名，但其对抗肿瘤免疫的影响尚不清楚。因此，我们制备了温石棉B（CB）石棉暴露的YT-A1人NK细胞亚系（YT-CB 5）作为体外模型，分析石棉暴露对NK细胞的影响，并检测其细胞毒性及其相关分子的表达。YT-CB 5对K562细胞的杀伤活性较YT-A1（YT-CB 5）降低。YT-CB 5细胞表面NKG 2D、2134和细胞内颗粒酶A的表达显著降低。YT-CB 5还表现出2B4依赖性细胞毒性的降低。此外，通过细胞表面NKG2D和2134刺激的脱颗粒也在YT-CB 5中减少。因此，恶性间皮瘤（MM）患者的外周血NK细胞进行了检查，并与健康志愿者进行比较。MM患者的NK细胞对K562的细胞毒性也有所降低。MM患者NK细胞中NKG2D和2B4的表达虽未降低，但细胞表面NKp46的表达降低。为了确认石棉暴露对外周血NK细胞的影响，在暴露于CB的情况下培养了PBMCs。在体外暴露于CB的PBMC中的NK细胞显示出NKp46表达的显著降低，而暴露于玻璃棉的PBMC中的NK细胞没有显示出这种降低。这些结果表明，暴露于石棉有可能损害NK细胞的细胞毒性，并改变NK细胞活化受体（包括NKG2D、2114和NKp46）和细胞内穿孔素/颗粒酶的表达。
Asbestos is well-known for its tumorigenic activity, but its effect on anti-tumor immunity remains unclear. Therefore, we prepared a sub-line of YT-A1 human NK cells exposed to chrysotile B (CB) asbestos (YT-CB5) as an in vitro model to analyze the effect of asbestos exposure on NK cells, and examined cytotoxicity and expressions of its related molecules. The cytotoxicity of YT-CB5 against K562 cells decreased compared with the original line of YT-A1 (YT-Org). YT-CB5 exhibited significant decreases in expressions of cell surface NKG2D, 2134 and intracellular granzyme A. YT-CB5 also exhibited a decrease in the 2B4-dependent cytotoxicity. In addition, the degranulations stimulated via cell surface NKG2D and 2134 also decreased in YT-CB5. Therefore, peripheral blood NK cells in patients with malignant mesothelioma (MM) were examined and compared with healthy volunteers. NK cells in patients with MM also showed decreases in cytotoxicity against K562. Although the expressions of NKG2D and 2B4 did not decrease in NK cells of MM patients, the expression of cell surface NKp46 decreased. To confirm the effect of asbestos exposure on peripheral blood NK cells, PBMCs were cultured under exposure to CB. NK cells in PBMCs exposed to CB in vitro showed a significant decrease in the expression of NKp46, whereas NK cells in PBMCs exposed to glass wool did not show such a decrease. These results indicate that exposure to asbestos has the potential to impair the cytotoxicity of NK cells and alter the expression of NK cell-activating receptors including NKG2D, 2114 and NKp46 and intracellular perforin/granzymes.