重组高迁移率族蛋白1(rHMGB1)体外诱导小鼠骨髓细胞向髓源性抑制性细胞(MDSC)分化  

Recombinant HMGB1 induces the differentiation of mouse myeloid cells into myeloid-derived suppressor cells in vitro

作　　者：苏兆亮[1] 张永健[1] 倪萍[1] 王佳[1] SU Zhaoliang ZHANG Yongjian NI Ping WANG Jia(Department of Immunology, Jiangsu University, Zhenjiang 212013, China)

机构地区：[1]江苏大学免疫学研究室,江苏镇江212013

出　　处：《细胞与分子免疫学杂志》2016年第10期1362-1365,1371,共5页Chinese Journal of Cellular and Molecular Immunology

基　　金：江苏省六大人才高峰项目(2013-WSN-002)

摘　　要：目的探讨重组高迁移率族蛋白1(r HMGB1)对髓源性抑制性细胞(MDSC)的体外分化作用。方法分离BALB/c小鼠的骨髓细胞,分别使用r HMGB1、粒细胞-巨噬细胞集落刺激因子联合白细胞介素6(GM-CSF-IL-6)、GM-CSF、IL-6和r HMGB1三者联合(GM-CSF-IL-6-r HMGB1)进行体外刺激48 h,流式细胞术检测CD11b+Gr1+MDSC、CD11c+和F4/80+巨噬细胞的比例。用免疫磁珠体外分选出粒细胞源性MDSC(G-MDSC)和巨噬细胞源性MDSC(M-MDSC)分别用r HMGB1刺激48 h,流式细胞术检测各组细胞中CD11b+Gr1+MDSC、CD11c+细胞和F4/80+巨噬细胞的比例。结果与对照组相比,r HMGB1、GM-CSF-IL-6、GM-CSF-IL-6-HMGB1刺激48 h后,CD11b+Gr1+MDSC比例增加,CD11c+细胞和F4/80+巨噬细胞的比例减少;免疫磁珠体外分选出G-MDSC和M-MDSC,用r HMGB1蛋白刺激48 h,与对照组相比,r HMGB1刺激后,CD11b+Gr1+MDSC、CD11c+细胞和F4/80+巨噬细胞的比例无显著性差异。结论 r HMGB1体外可以诱导分化MDSC比例增加,GM-CSF、IL-6与r HMGB1联用可以增强诱导效果。Objective To investigate the effects of recombinant high mobility group box l（ r HMGB1） on the differentiation of myeloid-derived suppressor cells（ MDSCs） in vitro. Methods The cel s were harvested from the bone marrow of BALB / c mice and cultured with r HMGB1, granulocyte-macrophage colony-stimulating factor（ GM-CSF） combined with IL-6（ GM-CSF-IL-6）,GM-CSF combined with IL-6 and r HMGB1（ GM-CSF-IL-6-r HMGB1）,separately in vitro. The percentages of CD11b＋Gr1＋MDSCs,CD11c＋cells and F4 /80＋macrophages were measured by flow cycometry（ FCM） after treatment for 48 hours. Monocytic MDSCs（ M-MDSCs） and granulocytic MDSCs（ G-MDSCs） were isolated from the femurs of healthy BALB / c mice,and then stimulated with r HMGB1. The proportions of CD11b＋Gr1＋MDSCs,CD11c＋cells and F4 /80＋macrophages were detected by FCM. Results FCM showed that the proportions of CD11b＋Gr1＋MDSCs in r HMGB1 group,GM-CSF-IL-6 group,GM-CSF-IL-6-HMGB1 group increased,while CD11c＋cells and F4 /80＋macrophages decreased as compared with control group after 48 hours. Following r HMGB1 treatment,the percentages of M-MDSCs and G-MDSCs were raised and the proportions of CD11c＋cells and F4 /80＋macrophages were reduced in r HMGB1-treated group,but there were no significant differences between M-MDSCs and G-MDSCs groups. Conclusion The r HMGB1 can induce MDSC differentiation; r HMGB1 combined with GM-CSF and IL-6 can more effectively promote MDSC differentiation in vitro.

关 键 词：高迁移率族蛋白1(HMGB1) 髓源性抑制细胞 分化 

分 类 号：R392.12[医药卫生—免疫学] Q254[医药卫生—基础医学]