Human CD68 promoter GFP transgenic mice allow analysis of monocyte to macrophage differentiation in vivo
Human CD68 promoter GFP transgenic mice allow analysis of monocyte to macrophage differentiation in vivo
复制标题
DOI：
10.1182/blood-2014-04-568691
复制
发表时间：
2014-10-09
期刊：
影响因子：
20.3
通讯作者：
Greaves, David R.
中科院分区：
文献类型：
--
作者：
Iqbal, Asif J.;McNeill, Eileen;Greaves, David R.
单核细胞的募集及其在炎症部位分化为巨噬细胞是决定炎症反应结果和启动恢复组织稳态的关键事件。为了研究体内单核细胞的运输和巨噬细胞的分化，我们已经产生了一种新的转基因报告小鼠表达的绿色荧光蛋白（GFP）的人CD 68启动子的控制下。CD 68-GFP小鼠在成年动物的单核细胞和胚胎来源的组织驻留巨噬细胞中表达高水平的GFP。人CD 68启动子驱动GFP在成人血液、脾脏和骨髓的所有CD 115（+）单核细胞中表达;我们利用这一点，使用无菌酵母多糖腹膜炎模型，直接比较骨髓来源的CD 68-GFP单核细胞与CX（3）CR 1（GFP）单核细胞在体内的运输。与CX（3）CR 1（GFP）单核细胞在该模型中分化为巨噬细胞时下调GFP表达不同，CD 68-GFP单核细胞在分化为巨噬细胞后72小时内保持高水平的GFP表达，从而允许在炎症消退期间继续进行细胞追踪。总之，这种新的CD 68-GFP转基因报告小鼠系代表了用于分析单核细胞动员和单核细胞运输以及研究急性和慢性炎症模型中募集的单核细胞的命运的强大资源。
The recruitment of monocytes and their differentiation into macrophages at sites of inflammation are key events in determining the outcome of the inflammatory response and initiating the return to tissue homeostasis. To study monocyte trafficking and macrophage differentiation in vivo, we have generated a novel transgenic reporter mouse expressing a green fluorescent protein (GFP) under the control of the human CD68 promoter. CD68-GFP mice express high levels of GFP in both monocyte and embryo-derived tissue resident macrophages in adult animals. The human CD68 promoter drives GFP expression in all CD115(+) monocytes of adult blood, spleen, and bone marrow; we took advantage of this to directly compare the trafficking of bone marrow-derived CD68-GFP monocytes to that of CX(3)CR1(GFP) monocytes in vivo using a sterile zymosan peritonitis model. UnlikeCX(3)CR1(GFP) monocytes, which downregulate GFP expression on differentiation into macrophages in this model, CD68-GFP monocytes retain high-level GFP expression for 72 hours after differentiation into macrophages, allowing continued cell tracking during resolution of inflammation. In summary, this novel CD68-GFP transgenic reporter mouse line represents a powerful resource for analyzing monocyte mobilization and monocyte trafficking as well as studying the fate of recruited monocytes in models of acute and chronic inflammation.