载脂蛋白E基因缺失促进不成熟髓系细胞的增殖和向单核细胞的极化  

Apolipoprotein E Deficiency Promotes the Proliferation of Immature Myeloid Cells and Polarization of Monocytes

作　　者：童明宏[1,2] 孙奋勇[3] 罗瑞萍[2] 傅明杰[2] 李海涛[2] 王栋[2] 

机构地区：[1]同济大学医学院,上海市200336 [2]上海交通大学附属同仁医院,上海市200050 [3]同济大学附属第十人民医院,上海市200072

出　　处：《中国动脉硬化杂志》2014年第8期779-783,共5页Chinese Journal of Arteriosclerosis

基　　金：上海市长宁区科学技术委员会课题(CNKW2013J09);上海市科委浦江人才计划(12PJ1401700)资助

摘　　要：目的研究载脂蛋白E（ApoE）对小鼠骨髓来源的CD11b^＋Gr-1^＋髓系细胞增殖和分化的影响,阐述ApoE基因敲除小鼠（ApoE-/-）致动脉粥样硬化敏感的炎症相关新机制。方法 6-8周龄的ApoE-/-小鼠和C57/B6野生型小鼠,采用流式细胞术分析骨髓、脾脏和外周血中CD11b^＋Gr-1^＋髓系细胞、CD11b＋Gr-1-单核细胞和CD11b-Gr-1＋粒细胞的百分比的变化。应用定量RT-PCR和免疫荧光染色,鉴定ApoE基因和蛋白在CD11b^＋Gr-1^＋髓系细胞的表达。从骨髓分选CD11b^＋Gr-1^＋髓系细胞,体外培养24 h,流式细胞术分析ApoE基因缺失对髓系细胞周期改变的作用。结果 （1）ApoE基因缺失显著增加ApoE-/-小鼠外周血CD11b^＋Gr-1^＋髓系细胞和CD11b＋Gr-1-单核细胞;（2）ApoE基因缺失促进ApoE-/-小鼠脾脏和骨髓中CD11b^＋Gr-1^＋不成熟髓系细胞的增殖;（3）定量RT-PCR和免疫荧光染色证实ApoE在CD11b^＋Gr-1^＋髓系细胞有较高水平的表达;（4）ApoE基因缺失可以促进CD11b^＋Gr-1^＋细胞周期自G1期进入S期。结论ApoE基因缺失显著增加ApoE-/-小鼠脾脏和骨髓中CD11b^＋Gr-1^＋不成熟髓系细胞的增殖、巨噬细胞分化和动员。ApoE基因缺失促进CD11b^＋Gr-1^＋髓系细胞增殖与其促进细胞周期进入S期有关。Aim To investigate the role of apolipoprotein E（ ApoE） on the migration,proliferation,and differentiation of CD11b^＋Gr-1^＋immature myeloid cells with ApoE genetic deficiency mice. Methods CD11b^＋Gr-1^＋myeloid cells,CD11b＋Gr-1-monocytes,and CD11b-Gr-1＋granulocytes in the peripheral blood,spleen,and bone marrow of ApoE- /-mice and control C57 /B6 mice were analyzed by flow cytometry. Expression of ApoE in CD11b＋myeloid cells were examined by quantitative RT-PCR and immune-fluorescence co-staining with anti-CD11 b and anti-ApoE. Cell cycle analysis was performed by flow cytometry. Results（ 1） Genetic deficiency of ApoE markedly promoted the migration of multiple myeloid subsets,in particular CD11b^＋Gr-1^＋myeloid cells and CD11b＋Gr-1-monocytes.（ 2） Genetic deficiency of ApoE significantly increased the percentage of CD11b^＋Gr-1^＋immature myeloid cells in the spleen and bone marrow of ApoE- /-mice compared with wild type mice.（ 3） ApoE was highly expressed in CD11b＋myeloid cells located in the spleen and bone marrow.（ 4） ApoE deficiency increased the percentage of CD11b^＋Gr-1^＋myeloid cells in S cell cycle. Conclusions ApoE deficiency significantly promotes the proliferation,differentiation,and migration of CD11b^＋Gr-1^＋immature myeloid cells in the spleen and bone marrow of ApoE- /-mice. Repressing the proliferation of CD11b^＋Gr-1^＋immature myeloid cells and macrophage differentiation through an ApoE dependent signal pathway may provide a novel sight on the treatment of atherosclerosis.

关 键 词：动脉粥样硬化 不成熟髓系细胞 载脂蛋白E 单核细胞 固有免疫细胞 

分 类 号：R363[医药卫生—病理学]