Regulation of microglial migration, phagocytosis, and neurite outgrowth by HO‐1/CO signaling
Regulation of microglial migration, phagocytosis, and neurite outgrowth by HO‐1/CO signaling
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DOI：
10.1002/dneu.22253
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发表时间：
2015-08
影响因子：
3
通讯作者：
H. Scheiblich;Gerd Bicker
中科院分区：
文献类型：
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作者：
H. Scheiblich;Gerd Bicker
在炎症条件下，清除感染和凋亡的神经元尸体是为神经元恢复创造有利环境的基本过程。小胶质细胞是中枢神经系统的常驻免疫细胞和主要的吞噬细胞，在激活时表现出多种细胞反应。在这里，我们通过功能分析研究了CO生成酶血红素加氧酶1 （HO‐1）如何影响BV‐2小胶质细胞迁移、碎片清除和人NT2神经元的神经突生长。在划伤实验中，刺激HO - 1活性可减弱小胶质细胞的迁移，在由脂多糖（LPS）激活的小胶质细胞和凋亡诱导的神经元组成的急性炎症细胞培养模型中，刺激HO - 1活性可减弱吞噬。在LPS刺激过程中，CO供体的应用阻止了NO的产生，减少了小胶质细胞的迁移和神经元碎片的吞噬。LPS激活的小胶质细胞不需要细胞与细胞表面直接接触就能抑制人类神经元的神经突伸长。通过施用外源CO或通过向HO提供底物血红素增加内部CO产量，神经突生长的抑制完全逆转。我们的研究结果表明，HO‐1/CO信号在小胶质细胞激活后具有重要的细胞保护作用。此外，它们支持CO释放化学剂治疗中枢神经系统过度炎症的治疗潜力。©2014 Wiley期刊公司中国生物医学工程学报（英文版），2015
Clearance of infected and apoptotic neuronal corpses during inflammatory conditions is a fundamental process to create a favorable environment for neuronal recovery. Microglia are the resident immune cells and the predominant phagocytic cells of the CNS, showing a multitude of cellular responses upon activation. Here, we investigated in functional assays how the CO generating enzyme heme oxygenase 1 (HO‐1) influences BV‐2 microglial migration, clearance of debris, and neurite outgrowth of human NT2 neurons. Stimulation of HO‐1 activity attenuated microglial migration in a scratch wound assay, and phagocytosis in a cell culture model of acute inflammation comprising lipopolysaccharide (LPS)‐activated microglia and apoptosis‐induced neurons. Application of a CO donor prevented the production of NO during LPS stimulation, and reduced microglial migration and engulfment of neuronal debris. LPS‐activated microglia inhibited neurite elongation of human neurons without requiring direct cell–cell surface contact. The inhibition of neurite outgrowth was totally reversed by application of exogenous CO or increased internal CO production through supply of the substrate hemin to HO. Our results point towards a vital cytoprotective role of HO‐1/CO signaling after microglial activation. In addition, they support a therapeutic potential of CO releasing chemical agents in the treatment of excessive inflammatory conditions in the CNS. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 75: 854–876, 2015