Distinct functions of chemokine receptor axes in the atherogenic mobilization and recruitment of classical monocytes.
Distinct functions of chemokine receptor axes in the atherogenic mobilization and recruitment of classical monocytes.
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DOI：
10.1002/emmm.201201717
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发表时间：
2013-03
影响因子：
11.1
通讯作者：
Weber, Christian
中科院分区：
文献类型：
--
作者：
Soehnlein, Oliver;Drechsler, Maik;Doering, Yvonne;Lievens, Dirk;Hartwig, Helene;Kemmerich, Klaus;Ortega-Gomez, Almudena;Mandl, Manuela;Vijayan, Santosh;Projahn, Delia;Garlichs, Christoph D.;Koenen, Rory R.;Hristov, Mihail;Lutgens, Esther;Zernecke, Alma;Weber, Christian
我们使用了一种新的方法，细胞抑制诱导白细胞耗竭和随后的重建与白细胞剥夺经典（炎性/Gr 1hi）或非经典（居民/Gr 1 lo）单核细胞解剖他们的分化作用，在高脂饮食（HFD）下动脉粥样硬化进展。载脂蛋白E缺陷（Apoe−/−）小鼠缺乏经典单核细胞，但非经典单核细胞显示病变大小和巨噬细胞和凋亡细胞含量减少。相反，HFD诱导血液和骨髓中经典单核细胞的选择性扩增。增加CXCL 1水平伴随着其受体CXCR 2在经典单核细胞上的更高表达和通过CXCL 1中和对单核细胞增多的抑制，表明CXCL 1/CXCR 2轴在高胆固醇血症期间动员经典单核细胞中的优先作用。在基因缺陷型Apoe−/−小鼠中，将循环和病变经典单核细胞、基因缺陷型细胞的过继转移和颈动脉活体显微镜检查期间的药理学调节相关联的研究揭示了CCR 1和CCR 5而不是CCR 2或CX 3CR 1在经典单核细胞募集到动脉粥样硬化血管中的关键功能。总的来说，这些数据确立了经典单核细胞对动脉粥样硬化进展的影响，确定了CXCL 1在其动员中的顺序作用和CCR 1/CCR 5在其募集中的顺序作用。
We used a novel approach of cytostatically induced leucocyte depletion and subsequent reconstitution with leucocytes deprived of classical (inflammatory/Gr1hi) or non-classical (resident/Gr1lo) monocytes to dissect their differential role in atheroprogression under high-fat diet (HFD). Apolipoprotein E-deficient (Apoe−/−) mice lacking classical but not non-classical monocytes displayed reduced lesion size and macrophage and apoptotic cell content. Conversely, HFD induced a selective expansion of classical monocytes in blood and bone marrow. Increased CXCL1 levels accompanied by higher expression of its receptor CXCR2 on classical monocytes and inhibition of monocytosis by CXCL1-neutralization indicated a preferential role for the CXCL1/CXCR2 axis in mobilizing classical monocytes during hypercholesterolemia. Studies correlating circulating and lesional classical monocytes in gene-deficient Apoe−/− mice, adoptive transfer of gene-deficient cells and pharmacological modulation during intravital microscopy of the carotid artery revealed a crucial function of CCR1 and CCR5 but not CCR2 or CX3CR1 in classical monocyte recruitment to atherosclerotic vessels. Collectively, these data establish the impact of classical monocytes on atheroprogression, identify a sequential role of CXCL1 in their mobilization and CCR1/CCR5 in their recruitment.
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影响因子：
5.5
作者：
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通讯作者：
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