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Effect of ziram on natural killer, lymphokine-activated killer, and cytotoxic T lymphocyte activity

机译:齐拉姆对自然杀手,淋巴因子激活的杀手和细胞毒性T淋巴细胞活性的影响

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Ziram is a carbamate pesticide, which is widely used throughout the world as a fungicide in agriculture and as an accelerating agent in latex production. In the present study, we investigated the effect of ziram at 0.031–4 μM in vitro on human natural killer (NK) and lymphokine-activated killer (LAK) and murine cytotoxic T lymphocyte (CTL) activity and found that it significantly inhibited all three activities in a concentration-dependent manner. To explore the mechanism of ziram-induced inhibition of NK activity, NK-92MI cells, a human NK cell line, were used. We previously confirmed that NK-92MI cells express CD56, perforin, granzyme (Gr) A, GrB, Gr3/K, and granulysin and are highly cytotoxic to K562 cells in the chromium release assay. NK-92MI cells were treated with ziram at 0.125–4 μM for 4 or 16 h at 37°C in vitro. Then, intracellular levels of perforin, GrA, GrB, Gr3/K, and granulysin were determined by flow cytometry. It was found that ziram significantly reduced Gr3/K, granulysin, perforin, GrA, and GrB levels. The extent of the decrease differed among the proteins, and the order was as follows: Gr3/K > granulysin > perforin, GrA, and GrB. Taken together, these findings suggest the ziram-induced inhibition of NK, LAK, and CTL activities to be at least partially mediated by decreases in the intracellular levels of Gr3/K, granulysin, perforin, GrA, and GrB.
机译:Ziram是一种氨基甲酸酯农药,在世界范围内广泛用作农业杀真菌剂和乳胶生产中的促进剂。在本研究中,我们研究了体外剂量为0.031–4μM的ziram对人自然杀伤(NK)和淋巴因子激活的杀伤(LAK)以及鼠类细胞毒性T淋巴细胞(CTL)活性的影响,发现它显着抑制了所有这三种以浓度依赖的方式进行活动。为了探索ziram诱导的NK活性抑制机制,使用了NK-92MI细胞(一种人类NK细胞系)。我们先前确认NK-92MI细胞表达CD56,穿孔素,颗粒酶(Gr)A,GrB,Gr3 / K和颗粒溶素,并且在铬释放测定中对K562细胞具有高度的细胞毒性。 NK-92MI细胞在37°C下用0.125–4μM的ziram处理4或16 h。然后,通过流式细胞仪测定细胞内穿孔素,GrA,GrB,Gr3 / K和颗粒溶素的水平。发现ziram显着降低了Gr3 / K,颗粒溶素,穿孔素,GrA和GrB的水平。减少的程度因蛋白质而异,顺序如下:Gr3 / K>颗粒溶素>穿孔素,GrA和GrB。两者合计,这些发现表明,ziram诱导的NK,LAK和CTL活性的抑制至少部分地由细胞内Gr3 / K,颗粒溶素,穿孔素,GrA和GrB含量的降低介导。

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