PDF(Pubmed)
Abstract：
Microglia and macrophages can influence the evolution of myelin lesions through the production of extracellular vesicles (EVs). While microglial EVs promote in vitro differentiation of oligodendrocyte precursor cells (OPCs), whether EVs derived from macrophages aid or limit OPC maturation is unknown.
Immunofluorescence analysis for the myelin protein MBP was employed to evaluate the impact of EVs from primary rat macrophages on cultured OPC differentiation. Raman spectroscopy and liquid chromatography-mass spectrometry was used to define the promyelinating lipid components of myelin EVs obtained in vitro and isolated from human plasma.
Here we show that macrophage-derived EVs do not promote OPC differentiation, and those released from macrophages polarized towards an inflammatory state inhibit OPC maturation. However, their lipid cargo promotes OPC maturation in a similar manner to microglial EVs. We identify the promyelinating endocannabinoids anandamide and 2-arachidonoylglycerol in EVs released by both macrophages and microglia in vitro and circulating in human plasma. Analysis of OPC differentiation in the presence of the endocannabinoid receptor antagonists SR141716A and AM630 reveals a key role of vesicular endocannabinoids in OPC maturation. From this study, EV-associated endocannabinoids emerge as important mediators in microglia/macrophage-oligodendrocyte crosstalk, which may be exploited to enhance myelin repair.
Immunofluorescence analysis for the myelin protein MBP was employed to evaluate the impact of EVs from primary rat macrophages on cultured OPC differentiation. Raman spectroscopy and liquid chromatography-mass spectrometry was used to define the promyelinating lipid components of myelin EVs obtained in vitro and isolated from human plasma.
Here we show that macrophage-derived EVs do not promote OPC differentiation, and those released from macrophages polarized towards an inflammatory state inhibit OPC maturation. However, their lipid cargo promotes OPC maturation in a similar manner to microglial EVs. We identify the promyelinating endocannabinoids anandamide and 2-arachidonoylglycerol in EVs released by both macrophages and microglia in vitro and circulating in human plasma. Analysis of OPC differentiation in the presence of the endocannabinoid receptor antagonists SR141716A and AM630 reveals a key role of vesicular endocannabinoids in OPC maturation. From this study, EV-associated endocannabinoids emerge as important mediators in microglia/macrophage-oligodendrocyte crosstalk, which may be exploited to enhance myelin repair.
摘要：
■小胶质细胞和巨噬细胞可以通过产生细胞外囊泡（EV）来影响髓鞘病变的演变。虽然小胶质细胞促进少突胶质细胞前体细胞（OPCs）的体外分化，来自巨噬细胞的EV是否有助于或限制OPC成熟尚不清楚。
■采用髓鞘蛋白MBP的免疫荧光分析来评估来自原代大鼠巨噬细胞的EV对培养的OPC分化的影响。拉曼光谱和液相色谱-质谱法用于定义体外获得并从人血浆中分离的髓磷脂EV的髓鞘形成脂质成分。
■在这里，我们表明巨噬细胞衍生的电动汽车不促进OPC分化，和从巨噬细胞释放的极化向炎症状态抑制OPC成熟。然而,它们的脂质货物以类似于小胶质细胞EV的方式促进OPC成熟。我们在体外和人血浆中循环的巨噬细胞和小胶质细胞释放的电动汽车中鉴定了早幼粒细胞内源性大麻素anandamide和2-花生四酰基甘油。在内源性大麻素受体拮抗剂SR141716A和AM630存在下OPC分化的分析揭示了囊泡内源性大麻素在OPC成熟中的关键作用。从这项研究中,EV相关的内源性大麻素作为小胶质细胞/巨噬细胞-少突胶质细胞串扰的重要介质出现，可用于增强髓鞘修复。
■采用髓鞘蛋白MBP的免疫荧光分析来评估来自原代大鼠巨噬细胞的EV对培养的OPC分化的影响。拉曼光谱和液相色谱-质谱法用于定义体外获得并从人血浆中分离的髓磷脂EV的髓鞘形成脂质成分。
■在这里，我们表明巨噬细胞衍生的电动汽车不促进OPC分化，和从巨噬细胞释放的极化向炎症状态抑制OPC成熟。然而,它们的脂质货物以类似于小胶质细胞EV的方式促进OPC成熟。我们在体外和人血浆中循环的巨噬细胞和小胶质细胞释放的电动汽车中鉴定了早幼粒细胞内源性大麻素anandamide和2-花生四酰基甘油。在内源性大麻素受体拮抗剂SR141716A和AM630存在下OPC分化的分析揭示了囊泡内源性大麻素在OPC成熟中的关键作用。从这项研究中,EV相关的内源性大麻素作为小胶质细胞/巨噬细胞-少突胶质细胞串扰的重要介质出现，可用于增强髓鞘修复。
