McNeill Eileen, Iqbal Asif J, Jones Daniel, Patel Jyoti, Coutinho Patricia, Taylor Lewis, Greaves David R, Channon Keith M
From the Division of Cardiovascular Medicine, British Heart Foundation Centre for Research Excellence, Radcliffe Department of Medicine, John Radcliffe Hospital, United Kingdom (E.M., D.J., J.P., P.C., K.M.C.); Wellcome Trust Centre for Human Genetics, Headington, Oxford, United Kingdom (E.M., J.P., P.C., K.M.C.); and Sir William Dunn School of Pathology, University of Oxford, United Kingdom (A.J.I., L.T., D.R.G.).
Arterioscler Thromb Vasc Biol. 2017 Feb;37(2):258-263. doi: 10.1161/ATVBAHA.116.308367. Epub 2016 Dec 1.
To create a model of atherosclerosis using green fluorescent protein (GFP)-targeted monocytes/macrophages, allowing analysis of both endogenous GFP and adoptively transferred GFP myeloid cells in arterial inflammation. APPROACH AND RESULTS: hCD68GFP reporter mice were crossed with ApoE mice. Expression of GFP was localized to macrophages in atherosclerotic plaques and in angiotensin II-induced aortic aneurysms and correlated with galectin 3 and mCD68 expression. Flow cytometry confirmed GFP expression in CD11b/CD64, CD11c/MHC-II, and CD11b/F4/80 myeloid cells. Adoptive transfer of GFP monocytes demonstrated monocyte recruitment to both adventitia and atherosclerotic plaque, throughout the aortic root, within 72 hours. We demonstrated the biological utility of hCD68GFP monocytes by comparing the recruitment of wild-type and CCR2 monocytes to sites of inflammation.
hCD68GFP/ApoE mice provide a new approach to study macrophage accumulation in atherosclerotic plaque progression and to identify cells recruited from adoptively transferred monocytes.
利用绿色荧光蛋白(GFP)靶向的单核细胞/巨噬细胞创建动脉粥样硬化模型,以便在动脉炎症中分析内源性GFP和过继转移的GFP髓系细胞。方法与结果:hCD68GFP报告基因小鼠与载脂蛋白E(ApoE)小鼠杂交。GFP的表达定位于动脉粥样硬化斑块以及血管紧张素II诱导的主动脉瘤中的巨噬细胞,并且与半乳糖凝集素3和mCD68的表达相关。流式细胞术证实GFP在CD11b/CD64、CD11c/MHC-II和CD11b/F4/80髓系细胞中表达。GFP单核细胞的过继转移表明,在72小时内,单核细胞在整个主动脉根部的外膜和动脉粥样硬化斑块中均有募集。通过比较野生型和CCR2单核细胞向炎症部位的募集情况,我们证明了hCD68GFP单核细胞的生物学效用。
hCD68GFP/ApoE小鼠为研究巨噬细胞在动脉粥样硬化斑块进展中的积聚以及鉴定过继转移单核细胞募集的细胞提供了一种新方法。