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目的探讨曲古抑菌素A(TSA)对正常人外周血自然杀伤细胞(NK)活性和功能的影响。方法从正常人外周血单个核细胞(PBMCs)分离淋巴细胞(PBLs)(主要包括T细胞和NK细胞)或纯化NK细胞。体外应用白介素-2(IL-2)诱导PBLs 72 h产生淋巴因子激活的杀伤(LAK)细胞。将PBLs,LAK或NK细胞进行体外培养,给予不同浓度的TSA处理122、44、8 h。流式细胞术检测NK细胞和T细胞的凋亡;采用51Cr释放试验检测NK细胞的杀伤功能。结果TSA以剂量和时间依赖方式诱导PBLs和LAK细胞凋亡,TSA处理组淋巴细胞及LAK细胞凋亡百分率明显高于对照组(P<0.05);TSA同样可诱导静止期NK细胞的凋亡,0.1μmol/L TSA作用于NK细胞24 h后,36%NK细胞凋亡,显著高于未处理组(P<0.05);0.1μmol/L TSA作用于NK细胞12 h后,其杀伤白血病细胞的能力明显低于对照组(P<0.01)。结论TSA能够诱导人外周血静止期NK细胞及LAK细胞发生凋亡,并影响NK细胞的细胞毒作用。
Objective To investigate the effect of trichostatin A (TSA) on the activity and function of natural killer (NK) cells in normal human. Methods PBLs (mainly including T cells and NK cells) or purified NK cells were isolated from normal human peripheral blood mononuclear cells (PBMCs). In vitro, interleukin-2 (IL-2) was used to induce PBLs to produce lymphokine activated killer (LAK) cells for 72 h. PBLs, LAK or NK cells were cultured in vitro, with different concentrations of TSA treatment 122,44,8 h. Flow cytometry was used to detect the apoptosis of NK cells and T cells. The cytotoxicity of NK cells was detected by 51Cr release assay. Results TSA induced the apoptosis of PBLs and LAK cells in a dose-and time-dependent manner. The percentages of TSA-treated lymphocytes and LAK cells were significantly higher than those of the control group (P <0.05). TSA also induced apoptosis of resting NK cells, After being treated with 0.1μmol / L TSA for 24 hours, NK cell apoptosis in 36% of NK cells was significantly higher than that in untreated cells (P <0.05). After treated with 0.1μmol / L TSA for 12 hours, NK cells could kill leukemic cells Ability was significantly lower than the control group (P <0.01). Conclusion TSA can induce the apoptosis of NK cells and LAK cells in peripheral blood and affect the cytotoxicity of NK cells.