Plasmacytoid Dendritic Cells Play a Key Role in Promoting Atherosclerosis in Apolipoprotein E-Deficient Mice
Plasmacytoid Dendritic Cells Play a Key Role in Promoting Atherosclerosis in Apolipoprotein E-Deficient Mice
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DOI：
10.1161/atvbaha.112.251314
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发表时间：
2012-11-01
影响因子：
8.7
通讯作者：
Maffia, Pasquale
中科院分区：
文献类型：
--
作者：
MacRitchie, Neil;Grassia, Gianluca;Maffia, Pasquale
目的：临床研究证实，循环中浆细胞样树突状细胞(PDCs)数量减少是冠状动脉疾病心血管事件的预测因子，pDCs在人类动脉粥样硬化斑块的肩部可检测到，在那里最有可能发生破裂。动物模型的结果是有争议的，PDCs被认为是抑制还是促进病变的发展，这取决于实验设置。在此，我们研究了pDC在载脂蛋白E缺陷小鼠动脉粥样硬化中的作用。方法和结果-我们证明载脂蛋白E缺陷小鼠和C57BL/6小鼠的动脉和脾都有相似数量的pDC，具有相似的激活状态。相反，使用Eα/Y-Ae系统对抗原摄取/提呈的评估显示，载脂蛋白E缺陷小鼠的主动脉pDC能够递送体内全身给药的抗原。持续用抗小鼠浆细胞样树突状细胞抗原1(mPDCA-1)抗体治疗载脂蛋白E缺陷小鼠，可导致动脉和脾中pDCs的特异性耗竭，并显著减少主动脉窦内动脉粥样硬化的形成(46%；P
Objective-Clinical studies have identified that reduced numbers of circulating plasmacytoid dendritic cells (pDCs) act as a predictor of cardiovascular events in coronary artery disease and that pDCs are detectable in the shoulder region of human atherosclerotic plaques, where rupture is most likely to occur. Results from animal models are controversial, with pDCs seen to inhibit or promote lesion development depending on the experimental settings. Here, we investigated the role of pDCs in atherosclerosis in apolipoprotein E-deficient mice.Methods and Results-We demonstrated that the aorta and spleen of both apolipoprotein E-deficient and C57BL/6 mice displayed similar numbers of pDCs, with similar activation status. In contrast, assessment of antigen uptake/presentation using the E alpha/Y-Ae system revealed that aortic pDCs in apolipoprotein E-deficient-mice were capable of presenting in vivo systemically administered antigen. Continuous treatment of apolipoprotein E-deficient mice with anti-mouse plasmacytoid dendritic cell antigen 1 (mPDCA-1) antibody caused specific depletion of pDCs in the aorta and spleen and significantly reduced atherosclerosis formation in the aortic sinus (by 46%; P