高三尖杉酯碱联合IFNα-2b可促进白血病源性树突状细胞成熟  

Homoharringtonine and interferon α-2b promote maturation of leukemic dendritic cells derived from K562/A02 cells

作　　者：孔德晓[1,2] 陈春燕[1] 王涓冬[1,2] 于晓林[1] 

机构地区：[1]山东大学齐鲁医院血液科,山东济南250012 [2]山东大学第二医院血液科,山东济南250033

出　　处：《中国病理生理杂志》2009年第8期1517-1521,共5页Chinese Journal of Pathophysiology

基　　金：山东省科技攻关重点课题资助项目(No.2004GG2202107);山东省优秀中青年科学家奖励基金资助项目(No.2004BS02007);第五批山东省卫生系统"1020"科技人才工程资助项目

摘　　要：目的:研究高三尖杉酯碱(HHT)、干扰素α-2b(IFNα-2b)和两者联合(HHT+IFNα-2b)对白血病源性树突状细胞(DCs)的促成熟作用。方法:在白血病多药耐药细胞K562/A02中加入细胞因子rhGM-CSF和rhIL-4,7d后Wright-Gimsa染色观察细胞形态的变化,流式细胞术检测细胞免疫表型的变化,同种混合淋巴细胞反应、CTL杀伤效应、细胞因子IL-12的分泌来评价此白血病源性DC的成熟程度,然后在上述白血病源性DC中分别加入HHT、IFNα-2b和HHT+IFNα-2b,3d后以上述同样方法检测它们对此白血病源性DC的促成熟作用。结果:K562/A02细胞在rhGM-CSF和rhIL-4作用7d后,CD83、HLA-DR和CD86分子的表达分别为(65.50±8.40)%、(32.00±4.32)%和(18.65±3.20)%,经HHT作用后这3种分子的表达升高到(85.36±8.42)%、(39.58±7.68)%和(35.53±4.35)%;经IFNα-2b作用后升高到(87.15±7.59)%、(40.53±6.30)%和(38.45±6.42)%;经HHT+IFNα-2b联合作用后升高到(94.38±6.59)%、(52.75±8.51)%和(42.98±9.87)%,与作用前相比差异均显著。经HHT、IFNα-2b和HHT+IFNα-2b作用后具有典型DC形态的细胞增多。经HHT和IFNα-2b作用的DC均可刺激T细胞产生较强的增殖效应,诱导产生的CTL对靶细胞K562/A02的杀伤率明显增强且当效靶比为20:1时杀伤效率最强,IL-12分泌明显增高。结论:HHT和IFNα-2b对白血病源性DC有促成熟作用,且两者联用时作用最强。AIM： To study the maturational effect of homoharringtonine （HHT） and interferon α-2b on leukemia - derived dendritic cells （DCs）. METHODS ： Cytokines rhGM - CSF and rhIL - 4 were added into the leukemia cells K562/A02. After 7 d induction, the cell - morphology was observed with the inverted microscope, the immunophenotype of cells was detected by flow cytometry and the cell function was evaluated by allogeneic mixed lymphocyte reactions, CTL responses and secretion of IL - 12. Then homoharringtonine, interferon α-2b and homoharringtonine ＋ interferon α- 2b were added to these leukemia -derived DCs： Three days later, the DCs were redetected by the above -mentioned methods. RESULTS： After induced by homoharringtonine and interferon α-2b, the leukemia - derived DCs with typical den- dritic morphology were increased. The expressions of CD83, HLA - DR and CD86 were （65.50± 8. 40） %, （ 32. 00±4. 32）% and （ 18.65± 3.20）% respectively in 7 d leukemia - derived DCs, raised to （85. 36±8. 42）%, （39. 58 ± 7. 68）% and （35. 53 ± 4. 35 ）% respectively after exposing to homoharringtonine for 3 d, and increased to （87. 15 ±7. 59） %, （40. 53 ± 6. 30） % and （ 38. 45 ± 6. 42） % respectively after treated by interferon ot - 2b ; and further increased to （94. 38± 6. 59） %, （52. 75 ± 8.51 ） % and （42. 98 ± 9. 87 ） % respectively after treated by homoharringtonine ＋ interferon α -2b. These results were markedly different from unaffected cells. These DCs induced by HHT and interferon α -2b were upregulated significantly the capacity for stimulating allogeneic T cells. They also induced CTL to generate specific cytotoxic activity against K562/A02 cells and there was the strongest effect when the ratio of effector and targetor was 20： 1. The secretion of IL -12 was increased remarkably. CONCLUSION： Homoharringtonine and interferon α-2b induce the maturation of the leukemia -derived DCs and there is the strongest function when homoharringtonine coope

关 键 词：高三尖杉酯碱 干扰素Α-2B 树突细胞 K562/A02细胞 

分 类 号：R551[医药卫生—血液循环系统疾病]