Li Qing, Kawada Tomoyuki
Department of Hygiene and Public Health, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan.
Cell Mol Immunol. 2006 Jun;3(3):171-8.
The main toxicity of organophosphorus pesticides (OPs) is neurotoxicity, which is caused by the inhibition of acetylcholinesterase. OPs also affect immune responses including effects on antibody production, IL-2 production, T cell proliferation, decrease of CD5 cells, and increase of CD26 cells and autoantibodies. However, there have been few papers investigating the mechanism of OP-induced inhibition of cytolytic activity of killer cells. This study reviews the new mechanism of OP-induced inhibition of activities of natural killer (NK), lymphokine-activated killer (LAK) and cytotoxic T lymphocytes (CTL). NK, LAK and CTL induce cell death in tumor or virus-infected target cells by two main mechanisms. The first mechanism is direct release of cytolytic granules that contain perforin, granzymes, and granulysin by exocytosis to kill target cells, which is called the granule exocytosis pathway. The second mechanism is mediated by the Fas ligand (Fas-L)/Fas pathway. To date, it has been reported that OPs inhibit NK, LAK and CTL activities by at least the following three mechanisms: 1) OPs impair the granule exocytosis pathway of NK, LAK and CTL cells by inhibiting the activity of granzymes, and by decreasing the intracellular level of perforin, granzyme A and granulysin, which was mediated by inducing degranulation of NK cells and by inhibiting the transcript of mRNA of perforin, granzyme A and granulysin; 2) OPs impair the FasL/Fas pathway of NK, LAK and CTL cells, as investigated by using perforin-knockout mice, in which the granule exocytosis pathway of NK cells does not function and only the FasL/Fas pathway remains functional; 3) OPs induce apoptosis of immune cells.
有机磷农药(OPs)的主要毒性是神经毒性,它由乙酰胆碱酯酶的抑制作用引起。OPs还会影响免疫反应,包括对抗体产生、白细胞介素-2产生、T细胞增殖、CD5细胞减少以及CD26细胞和自身抗体增加的影响。然而,很少有论文研究OP诱导杀伤细胞溶细胞活性抑制的机制。本研究综述了OP诱导自然杀伤(NK)细胞、淋巴因子激活的杀伤(LAK)细胞和细胞毒性T淋巴细胞(CTL)活性抑制的新机制。NK细胞、LAK细胞和CTL细胞通过两种主要机制诱导肿瘤或病毒感染的靶细胞死亡。第一种机制是通过胞吐作用直接释放含有穿孔素、颗粒酶和颗粒溶素的溶细胞颗粒来杀死靶细胞,这被称为颗粒胞吐途径。第二种机制由Fas配体(Fas-L)/Fas途径介导。迄今为止,已有报道称OPs至少通过以下三种机制抑制NK细胞、LAK细胞和CTL细胞的活性:1)OPs通过抑制颗粒酶的活性,以及通过降低穿孔素、颗粒酶A和颗粒溶素的细胞内水平来损害NK细胞、LAK细胞和CTL细胞的颗粒胞吐途径,这是由诱导NK细胞脱颗粒以及抑制穿孔素、颗粒酶A和颗粒溶素的mRNA转录介导的;2)通过使用穿孔素基因敲除小鼠进行研究发现,OPs损害NK细胞、LAK细胞和CTL细胞的FasL/Fas途径,在这种小鼠中NK细胞的颗粒胞吐途径不起作用,仅FasL/Fas途径保持功能;3)OPs诱导免疫细胞凋亡。