曲古抑菌素A对外周血自然杀伤细胞活性和功能的影响

Effects of trichostatin A effects on natural killer cell survival and activity

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 explore the potential regulatory effects of trichostatin A(TSA) on survival and activity of natural killer(NK) cells.Methods Human peripheral blood lymphocytes(PBLs)or NK cells were separated or isolated from peripheral blood mononuclear cells(PBMCs) of healthy blood donors.Lymphokine activated killer(LAK) cells were generated by culturing PBLs in the presence of interleukin-2 for 72 h.The cells were cultured in the presence or absence of TSA at the concentrations(0.01,0.1 and/or 1 μmol/L)for 1...