Class A scavenger receptor promotes cerebral ischemic injury by pivoting microglia/macrophage polarization
Class A scavenger receptor promotes cerebral ischemic injury by pivoting microglia/macrophage polarization
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DOI：
10.1016/j.neuroscience.2012.05.036
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发表时间：
2012-08
期刊：
影响因子：
3.3
通讯作者：
Yiming Xu;L. Qian;Guijuan Zong;K. Ma;Xudong Zhu;Hanwen Zhang;N. Li;Qing Yang;H. Bai
中科院分区：
文献类型：
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作者：
Yiming Xu;L. Qian;Guijuan Zong;K. Ma;Xudong Zhu;Hanwen Zhang;N. Li;Qing Yang;H. Bai
A类清道夫受体（SR-A）主要表达于小胶质细胞/巨噬细胞中，在免疫应答中起重要作用。然而，SR-A是否可以影响脑缺血损伤中的小胶质细胞/巨噬细胞极化尚不清楚。为此，我们监测了脑缺血损伤动物模型中小胶质细胞/巨噬细胞的表型改变。大脑中动脉永久性闭塞（MCAO）后24 h，SR-A在小鼠脑内表达上调。与野生型小鼠同窝对照组相比，SR-A缺陷小鼠显示梗死面积减少和神经功能改善。此外，在SR-A基因敲除小鼠的缺血性脑中，发现炎性F4/80+ CD 11 B + CD 45 highCD 11 c+小胶质细胞/巨噬细胞减少，核因子-κB（NF-κB）活化减弱。这伴随着经典活化的M1巨噬细胞标志物的减轻和替代活化的M2巨噬细胞标志物的保留。这些数据表明，SR-A有助于脑缺血性损伤的小胶质细胞/巨噬细胞的表型旋转到一个歪斜的M1极化。
Class A scavenger receptor (SR-A) is primarily expressed in microglia/macrophages and plays an important role in immune responses. However, whether SR-A can influence microglia/macrophage polarization in cerebral ischemic injury is not known. To this end we monitored the phenotypic alteration of microglia/macrophages in an animal model of cerebral ischemia injury. SR-A was up-regulated in mouse brains 24h after permanent occlusion of middle cerebral artery (MCAO). SR-A-deficient mice displayed reduced infarct size and improved neurological function compared with wild-type mice littermate controls. Furthermore, a decrease in inflammatory F4/80+CD11b+CD45highCD11c+microglia/macrophages and attenuated nuclear factor-kappaB (NF-κB) activation was found in ischemic brains in the SR-A null mice. This was accompanied by alleviation of classically activated M1 macrophage markers and preservation of alternatively activated M2 macrophage markers. These data suggest that SR-A contributes to cerebral ischemic injury by pivoting the phenotype of microglia/macrophages to a skewed M1 polarization.