Plasma Hemopexin ameliorates murine spinal cord injury by switching microglia from the M1 state to the M2 state.
Plasma Hemopexin ameliorates murine spinal cord injury by switching microglia from the M1 state to the M2 state.
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血浆血红素通过将小胶质细胞从 M1 状态切换到 M2 状态来改善小鼠脊髓损伤
DOI：
10.1038/s41419-017-0236-8
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发表时间：
2018-02-07
影响因子：
9
通讯作者：
He C
中科院分区：
文献类型：
--
作者：
Han D;Yu Z;Liu W;Yin D;Pu Y;Feng J;Yuan Y;Huang A;Cao L;He C
脊髓损伤（Spinal cord injury，SCI）是一种严重的中枢神经系统（central nervous system，CNS）损伤。小胶质细胞分化为M1或M2状态已被证实在SCI的发病机制中起重要作用，尽管尚未确定完整的潜在因素。有趣的是，脊髓血肿（脊髓髓内出血）缓解的时间点与M2小胶质细胞数量减少一致。在这里，血结合素（Hpx），一种血原性糖蛋白，在挤压模型的SCI中的功能进行了检查。在脊髓血肿期间，病变部位的Hpx水平升高，并与M2标记物精氨酸酶-1（Arg-1）的水平同步相关。体内Hpx的消融影响了脂多糖（LPS）刺激的小胶质细胞的极化状态，如损伤部位M2小胶质细胞百分比降低和M1小胶质细胞百分比升高所反映的，这延迟了SCI后的恢复并加剧了行为功能障碍。然而，在LPS刺激的原代培养的小胶质细胞中，Hpx诱导了从M1到M2表型的快速转换，其方式与血红素清除无关。Hpx处理的小胶质细胞上清液可改善神经元变性，减轻脱髓鞘，促进少突胶质前体细胞（OPC）成熟。Hpx对小胶质细胞极化的这种调节作用至少部分由LRP-1受体介导。基于这些结果，Hpx被认为是SCI发病过程中小胶质细胞极化的新调节剂，并可能在SCI的恢复中起关键作用。
Spinal cord injury (SCI) is a devastating type of central nervous system (CNS) trauma with limited therapeutic treatments. The polarization of microglia into the M1 or M2 state has been documented to play important roles in the pathogenesis of SCI, although the complete repertoire of underlying factors has not been identified. Interestingly, the time point at which hematomyelia (intramedullary spinal cord hemorrhage) is alleviated coincides with a decrease in the number of M2 microglia. Here the function of Hemopexin (Hpx), a hematogenous glycoprotein, was examined in the crush model of SCI. Hpx levels were elevated at the lesion site during hematomyelia and were synchronously correlated with the level of the M2 marker Arginase-1 (Arg-1). Ablation of Hpx in vivo affected the polarization state of lipopolysaccharide (LPS)-stimulated microglia, as mirrored by a lower percentage of M2 microglia and a higher percentage of M1 microglia in the lesion site, which delayed the recovery and exacerbated the behavioral dysfunction after SCI. However, Hpx induced a rapid switch from the M1 to M2 phenotype in LPS-stimulated primary cultured microglia in a heme scavenging-independent manner. The supernant of Hpx-treated microglia ameliorated neuronal degeneration, alleviated demyelination, and promoted oligodendrocyte precursor cell (OPC) maturation. This modulatory effect of Hpx on microglia polarization was at least partially mediated by the LRP-1 receptor. Based on these results, Hpx is considered a novel modulator of the polarization of microglia during the pathogenesis of SCI and may play a crucial role in the recovery from SCI.
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脑癌敲除小鼠中脑出血后纹状体损伤和行为缺陷增加。
影响因子：
4.1
作者：
Chen L;Zhang X;Chen-Roetling J;Regan RF
通讯作者：
Regan RF
影响因子：
15.3
作者：
Brambilla, R;Bracchi-Ricard, V;Hu, WH;Frydel, B;Bramwell, A;Karmally, S;Green, EJ;Bethea, JR
通讯作者：
Bethea, JR
影响因子：
4.2
作者：
Figley, Sarah A.;Khosravi, Ramak;Fehlings, Michael G.
通讯作者：
Fehlings, Michael G.
影响因子：
4.8
作者：
Hennen, Eva;Safina, Dina;Faissner, Andreas
通讯作者：
Faissner, Andreas
DOI：
10.1523/jneurosci.3257-09.2009
发表时间：
2009-10-28
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Kigerl KA;Gensel JC;Ankeny DP;Alexander JK;Donnelly DJ;Popovich PG
通讯作者：
Popovich PG