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首页> 外文期刊>Journal of Neuroimmunology: Official Bulletin of the Research Committee on Neuroimmunology of the World Federation of Neurology >Analysis of glial secretome: the long pentraxin PTX3 modulates phagocytic activity of microglia.
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Analysis of glial secretome: the long pentraxin PTX3 modulates phagocytic activity of microglia.

机译:神经胶质分泌物组的分析:长的五味素PTX3调节小胶质细胞的吞噬活性。

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摘要

Microglia, as the phagocytes of the central nervous system, play an important role in the recognition, engulfment, and clearance of apoptotic cells and invading microbes. Proteins secreted from activated glial cells may affect microglial phagocytic activity. Secreted proteins of mixed glial cells stimulated with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) for 24h were identified for the first time by liquid chromatography and tandem mass spectrometric analysis. Several proteins were newly identified as a glia-secreted protein. Among the proteins identified by the mixed glia secretome analysis, pentraxin 3 (PTX3) secretion was most highly induced by LPS/IFN-gamma stimulation. Expression of PTX3 mRNA was detected in primary microglia and astrocyte cultures as well as glial cell lines. Glial secretion of PTX3 and its inflammatory induction was confirmed by Western blot analysis of conditioned media of mixed glial cultures. PTX3 did not influence LPS-induced nitric oxide production or neurotoxicity of BV-2 microglial cells. Most importantly, PTX3 selectively modulated microglial phagocytosis activity; it promoted engulfment of zymosan particles, while it inhibited uptake of apoptotic cells. Our results indicate that glia-derived PTX3 may modulate phagocytic functions of microglia, and this may have important implications in the regulation of microglial activity in health and disease.
机译:小胶质细胞作为中枢神经系统的吞噬细胞,在凋亡细胞和入侵微生物的识别,吞噬和清除中起重要作用。活化的神经胶质细胞分泌的蛋白质可能会影响小胶质细胞的吞噬活性。通过液相色谱和串联质谱分析首次鉴定了用脂多糖(LPS)和干扰素-γ(IFN-γ)刺激24h的混合胶质细胞分泌的蛋白质。新鉴定出几种蛋白质为神经胶质分泌蛋白。在通过混合神经胶质细胞分泌物组分析鉴定的蛋白质中,LPS /IFN-γ刺激最能诱导五味素3(PTX3)分泌。在原发性小胶质细胞和星形胶质细胞培养以及胶质细胞系中检测到PTX3 mRNA的表达。通过对混合的神经胶质培养物的条件培养基进行蛋白质印迹分析,证实了PTX3的神经胶质分泌及其炎症诱导。 PTX3不会影响LPS诱导的一氧化氮生成或BV-2小胶质细胞的神经毒性。最重要的是,PTX3选择性调节小胶质细胞吞噬作用。它促进了酵母聚糖颗粒的吞噬,同时抑制了凋亡细胞的摄取。我们的结果表明,胶质细胞衍生的PTX3可能会调节小胶质细胞的吞噬功能,这可能对健康和疾病中小胶质细胞活性的调节具有重要意义。

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