LDLR缺失促进CD11b^+ Ly6C^+单核细胞的分化和CD11c^+树突状细胞的成熟  

LDLR deficiency promotes the differentiation of CD11b^+ Ly6C^+ monocytes and maturation of CD11c^+ dendritic cells

作　　者：童明宏[1] 张伟伟[2] 王向明[3] 张欢欢[1] 陶荣霞[1] 李盈[1] 丁素玲[2] 杨向东[2] 

机构地区：[1]上海交通大学医学院附属同仁医院检验科,上海市200336 [2]复旦大学附属中山医院心血管研究所,上海市200032 [3]上海交通大学医学院附属同仁医院神经内科,上海市200336

出　　处：《中国动脉硬化杂志》2017年第5期433-440,共8页Chinese Journal of Arteriosclerosis

基　　金：国家自然科学基金项目(91439121;81370402);高等学校博士学科点专项科研基金资助课题(20130071110042);上海市长宁区科学技术委员会项目(CNKW2013J09)

摘　　要：目的研究低密度脂蛋白受体敲除(LDLR^(-/-))对小鼠CD11b^+髓系免疫细胞增殖和分化的影响,探索异常免疫细胞反应在动脉粥样硬化发生中的炎症相关新机制。方法 6~8周龄的LDLR^(-/-)小鼠和对照野生型(WT)C57小鼠分别给予普通饮食和高脂饲养12周。采用流式细胞术分析外周血、脾脏和骨髓中免疫细胞亚群,尤其是CD11b^+Gr-1^+髓系免疫细胞、CD11b^+Ly6C+单核巨噬细胞和CD11b^+CD11c^+树突状细胞表达情况,同时检测Lin^-Sca-1^-CD34^+c Kit^+共同髓系祖细胞(CMP)在LDLR^(-/-)小鼠骨髓内表达情况。最后应用^(125)I标记anti-CD11b作为分子探针,在体无创监测LDLR^(-/-)小鼠主动脉粥样硬化斑块的炎症微环境。结果 (1)在普通饮食和高脂饲养状态下,LDLR缺失均可显著增加LDLR^(-/-)小鼠外周血和脾脏内CD11b^+和CD11b^+Gr-1^+髓系细胞的表达。(2)LDLR^(-/-)小鼠外周血和肝脏中CD11b^+Ly6C^+单核巨噬细胞的表达增加;CD11b^+CD11c^+树突状细胞在LDLR^(-/-)小鼠脾脏中的表达增加。(3)普通饮食状态下,CMP的百分比在LDLR^(-/-)小鼠骨髓中较WT小鼠增加,但在高脂饲养时减少。(4)以CD11b为炎症分子靶标,可用SPECT/CT实时监测LDLR^(-/-)小鼠动脉粥样斑块。结论 LDLR缺失显著增加CD11b^+Gr-1^+髓系免疫细胞的增殖和动员,促进LDLR^(-/-)小鼠单核巨噬细胞的分化和树突状细胞的成熟。以CD11b^+髓系细胞为靶标,可以在体监测动脉粥样斑块的炎症微环境。Aim To identify the role of low density lipoprotein receptor （LDLR） on the proliferation and differentiation of CD11b^＋ myeloid subsets, particularly CD11b^＋Gr-1^＋ immature myeloid cells with LDLR deficiency mice; To explore the mechanism of abnormal immune cell reaction in the pathogenesis of atherosclerosis. Methods 6-8 weeks old LDLR^-/- mice and control wild type （WT） C57 mice were fed with normal diet and high-fat diet for 12 weeks. Flow cytometry was used to analyze the subsets of immune cells in peripheral blood, spleen and bone marrow, especially the expressions of CD11b^＋Gr-1^＋ myeloid immune cell, CD11b^＋Ly6C^＋ mononuclear macrophage and CD11b^＋CD11c^＋ dendritic cell. Simultaneously the expression of Lin-Sca-1-CD34＋cKit＋ common myeloid progenitor （CMP） was detected in LDLR^-/- mouse bone marrow. Using 125I marker anti-CD11b as a molecular probe, inflammatory microenvironment of LDLR^-/- mice aortic atherosclerotic plaque was monitored noninvasively in vivo. Results （1）Under the condition of normal diet and high-fat diet, LDLR deficiency markedly enhanced the expressions CD11b^＋ and CD11b^＋Gr-1^＋ myeloid cells in peripheral blood and spleen of LDLR^-/- mice. （2）The expression of CD11b^＋Ly6C^＋ mononuclear macrophages increased in peripheral blood and liver of LDLR^-/- mice; The expression of CD11b^＋CD11c^＋ dendritic cells increased in the spleen of LDLR^-/- mice. （3）Under normal diet, the percentage of CMP was increased in LDLR^-/- mice bone marrow compared with WT mice, but decreased under high-fat diet. （4）Using CD11b as the molecular target of inflammation, SPECT/CT could be used to monitor the atherosclerotic plaque of LDLR^-/- mouse in real time. Conclusion LDLR deficiency significantly increases the proliferation and mobilization of CD11b^＋Gr-1^＋ myeloid immune cells, and promotes the differentiation of mononuclear macrophage and maturation of dendritic cell in LDLR^-/- mice. With CD11b^＋ myeloid cells as a target, the

关 键 词：动脉粥样硬化 低密度脂蛋白受体 不成熟髓系细胞 共同髓系祖细胞 单核巨噬细胞 树突状细胞 炎症 

分 类 号：R363[医药卫生—病理学]