Dimethyl 2,2-dichlorovinyl phosphate (DDVP) markedly decreases the expression of perforin, granzyme A and granulysin in human NK-92CI cell line
Dimethyl 2,2-dichlorovinyl phosphate (DDVP) markedly decreases the expression of perforin, granzyme A and granulysin in human NK-92CI cell line
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DOI：
10.1016/j.tox.2005.05.018
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发表时间：
2005-09-15
期刊：
影响因子：
4.5
通讯作者：
Kawada, T
中科院分区：
文献类型：
--
作者：
Li, Q;Nakadai, A;Kawada, T
自然杀伤细胞（NK）、淋巴因子激活杀伤细胞（LAK）和细胞毒性T淋巴细胞（CTL）细胞通过定向释放含有穿孔素、颗粒酶和颗粒蛋白的细胞溶解颗粒杀死靶细胞。我们之前发现有机磷农药二甲基2,2-二氯酰磷酸（DDVP）通过抑制颗粒酶活性显著抑制NK、LAK和CTL活性。为了进一步探讨有机磷农药诱导细胞介导的细胞溶解抑制的机制，我们研究了有机磷农药是否影响NK细胞穿孔素、颗粒酶和颗粒酶的表达。我们使用NK- 92ci细胞，一种不依赖白细胞介素-2 （IL-2）的人NK细胞系。我们通过流式细胞术和免疫荧光显微镜证实NK-92CI细胞表达CD56表面标记物、颗粒酶A和颗粒蛋白，并通过铬释放实验证实NK-92CI细胞对K562细胞具有高度的细胞毒性。我们发现DDVP显著降低NK-92CI细胞中perform、granzyme A和granulysin的表达，且呈剂量依赖性。免疫细胞化学结果显示，DDVP显著降低NK-92CI细胞的穿孔素、颗粒酶A和颗粒蛋白阳性颗粒，这可能与脱粒有关。我们还发现，DDVP对perform、granzyme a和granulysin mRNA的转录有适度但显著的抑制作用。2005爱思唯尔爱尔兰有限公司版权所有。
Natural killer (NK), lymphokine-activated killer (LAK) and cytotoxic T lymphocyte (CTL) cells kill target cells by the directed release of cytolytic granules that contain perforin, granzymes and granulysin. We previously have found that dimethyl 2,2-dichlorovinyl phosphate (DDVP), an organophosphorus pesticide significantly inhibited NK, LAK and CTL activities via the inhibition of granzyme activity. To further explore the mechanism of organophosphorus pesticide-induced inhibition of cell-mediated cytolysis, we asked here whether organophosphorus pesticides affect the expression of perforin, granzyme and granulysin in NK cells. We used NK-92CI cell, an interleukin-2 (IL-2) independent human NK cell line. We confirmed that NK-92CI cells express CD56 surface marker, perform, granzyme A and granulysin by flow cytometry and immunofluorescence microscope, and that it is highly cytotoxic to K562 cells in chromium release assay. We found that DDVP significantly decreases the expression of perform, granzyme A and granulysin in NK-92CI cells in a dose-dependent manner. Immunocytochemical results showed that DDVP significantly decreases perforin, granzyme A and granulysin positive granules in NK-92CI cell, which may be due to the degranulation. We also found that DDVP have a modest, but a significant inhibitory effect on the transcription of mRNA of perform, granzyme A and granulysin. (c) 2005 Elsevier Ireland Ltd. All rights reserved.