Extramedullary hematopoiesis generates Ly-6C(high) monocytes that infiltrate atherosclerotic lesions.
Extramedullary hematopoiesis generates Ly-6C(high) monocytes that infiltrate atherosclerotic lesions.
复制标题
外肺造血产生浸润动脉粥样硬化病变的LY-6C（高）单核细胞。
DOI：
10.1161/circulationaha.111.061986
复制
发表时间：
2012-01-17
期刊：
影响因子：
37.8
通讯作者：
Swirski FK
中科院分区：
文献类型：
--
作者：
Robbins CS;Chudnovskiy A;Rauch PJ;Figueiredo JL;Iwamoto Y;Gorbatov R;Etzrodt M;Weber GF;Ueno T;van Rooijen N;Mulligan-Kehoe MJ;Libby P;Nahrendorf M;Pittet MJ;Weissleder R;Swirski FK
动脉粥样硬化病变被认为是通过募集骨髓来源的单核细胞而生长的。在已知的小鼠单核细胞亚群中，Ly-6 Chigh单核细胞是炎性的，优先聚集在皮损中，并分化。在这里，我们假设在动脉粥样硬化期间，骨髓外包了Ly-6 Chigh单核细胞的产生。利用小鼠动脉粥样硬化模型和命运图方法，我们发现造血干细胞和祖细胞(HSPC)从骨髓逐渐迁移到脾红髓，在那里它们遇到GM-CSF和IL-3，克隆性扩增，并分化为Ly-6 Chigh单核细胞。在这种髓外壁龛中出生的单核细胞在动脉粥样斑块内大量聚集、循环和聚集。在皮损渗入时，Ly-6鸡单核细胞分泌炎性细胞因子、活性氧和蛋白水解酶。最终，它们摄取脂类，成为泡沫细胞。我们的发现表明，髓外部位通过产生渗入动脉粥样硬化病变的循环炎症细胞来补充骨髓的造血功能。
Atherosclerotic lesions are believed to grow via the recruitment of bone marrow-derived monocytes. Among the known murine monocyte subsets, Ly-6Chigh monocytes are inflammatory, accumulate in lesions preferentially, and differentiate. Here we hypothesized that the bone marrow outsources the production of Ly-6Chigh monocytes during atherosclerosis. Using murine models of atherosclerosis and fate-mapping approaches, we show that hematopoietic stem and progenitor cells (HSPC) progressively relocate from the bone marrow to the splenic red pulp where they encounter GM-CSF and IL-3, clonally expand, and differentiate to Ly-6Chigh monocytes. Monocytes born in such extramedullary niches intravasate, circulate, and accumulate abundantly in atheromata. Upon lesional infiltration, Ly-6Chigh monocytes secrete inflammatory cytokines, reactive oxygen species, and proteases. Eventually, they ingest lipids and become foam cells. Our findings indicate that extramedullary sites supplement the bone marrow’s hematopoietic function by producing circulating inflammatory cells that infiltrate atherosclerotic lesions.