粒细胞集落刺激因子对骨髓和外周血中骨髓来源的抑制细胞影响的初步研究

Effect of granulocyte colony stimulating factor on myeloid-derived suppressor cells in the bone marrow and peripheral blood:a preliminary study

目的探讨粒细胞集落刺激因子(G-CSF)用于造血干细胞动员对健康供者骨髓和外周血中骨髓来源的抑制细胞(MDSC)的影响和MDSC与移植物抗宿主疾病(GVHD)的关系。方法对12例健康造血干细胞供者,在G-CSF动员前和动员后第5天分别获取骨髓、外周血及外周血干细胞采集物,用流式细胞术检测其中MDSC的含量变化,统计分析MDSC与GVHD的关系。结果在正常生理状态下,健康供者外周血、骨髓中均能检测到MDSC,MDSC在外周血中占单个核细胞比例为(1.35±0.35)%,骨髓中为(2.44±1.11)%,骨髓中MDSC比外周血中高(P=0.015);G-CSF动员5d后MDSC在外周血中占单个核细胞比例为(4.01±1.82)%,骨髓中为(4.38±2.19)%,动员后骨髓与外周血中MDSC比例相比无明显变化(P=0.083)。动员后外周血中MDSC含量明显高于动员前(P=0.047),而动员前后骨髓MDSC细胞比例变化无统计学意义(P=0.761)。采集物中MDSC细胞数量与GVHD发生率呈明显负相关关系(P=0.048)。结论健康人PB与BM中均能检测到MDSC,且骨髓中比外周血中要高;G-CSF能动员骨髓中MDSC到达外周血,使外周血中MDSC增高;G-CSF动员的外周血干细胞采集物中MDSC增加与造血干细胞移植后低GVHD发生率有关。

Objective To investigate the effect of granulocyte colony stimulating factor（G-CSF） on myeloid-derived suppressor cells（MDSCs） in the bone marrow and peripheral blood,and explore the relationship between MDSC and graft-versus-host disease（GVHD）.Methods Bone marrow,peripheral blood and peripheral blood stem cells were obtained from 12 healthy hemopoietic stem cell donors before and on day 5 after G-CSF mobilization.Flow cytometry was employed to examine the number of MDSC,and the relationship between MDSC number and the incidence of GVHD was analyzed.Results In normal physiological conditions,MDSC could be detected in the peripheral blood and bone marrow with a cell percentages of（1.35 ± 0.35）% and（2.44 ± 1.11）% ,respectively,showing a significantly higher cell percentage in the bone marrow（P=0.015）.On the 5th day after G-CSF mobilization,the percentage of MDSCs increased to（4.01 ± 1.82）% in the peripheral blood and to（4.38 ± 2.19）% in the bone marrow,showing no significant difference between them（P=0.083）.The mobilization caused a significant increase in the number of MDSCs in the peripheral blood（P=0.047） but not in the bone marrow（P=0.761）.The number of MDSCs in the collected samples showed a significant inverse correlation to the incidence of GVHD（P=0.048）.Conclusions MDSCs are present in the peripheral blood and bone marrow of healthy donors,with a grater number in the bone marrow.G-CSF can mobilize the MDSCs from the bone marrow to the peripheral blood to increase number of MDSCs in the peripheral blood,which may contribute to a lowered incidence of GVHD in hematopoietic stem cell transplantation（HSCT）.