Nicholas R S, Wing M G, Compston A
University of Cambridge Neurology unit, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2QQ, UK.
Eur J Neurosci. 2001 Mar;13(5):959-67. doi: 10.1046/j.0953-816x.2001.01470.x.
We demonstrate a role for nonactivated rat microglia in the survival and maturation of oligodendrocyte precursor cells (OPCs). Media conditioned by nonactivated microglia increase the number of surviving galactocerebroside(+) (GalC(+)) oligodendrocytes in vitro at 48 h by inhibiting the apoptosis of OPCs and stimulating their maturation to GalC+ oligodendrocytes. These effects are not observed with medium conditioned by microglia activated with interferon-gamma (IFN-gamma). Conditioned medium from nonactivated microglia is associated with upregulation in OPCs of nuclear factor of kappa binding (NF-kappa B) p65 subunit. The use of antisense to the inhibitor of kappa binding (I kappa B) induces p65 subunit activation in OPCs and, in common with medium conditioned by nonactivated microglia, also inhibits OPC apoptosis and promotes cell maturation. Anti-platelet-derived growth factor (PDGF) antibody abolishes this effect even though PDGF-A chain is expressed at similar levels within both nonactivated and IFN-gamma-activated microglia and both conditioned media have similar levels of PDGF-A chain bioactivity. However, only conditioned medium from nonactivated microglia recruit phosphatidyl-3-inositol (PI-3) kinase to the PDGF-alpha receptor and synergise with endogenous PDGF-A chain to increase NF-kappa B activation. These results suggest that, dependent on their state of activation, microglia produce soluble factors that promote oligodendrocyte development through an effect on the PDGF-alpha receptor-signalling pathway.
我们证明了未激活的大鼠小胶质细胞在少突胶质前体细胞（OPC）的存活和成熟过程中发挥作用。未激活的小胶质细胞条件培养基通过抑制OPC凋亡并刺激其成熟为半乳糖脑苷脂阳性（GalC+）少突胶质细胞，在48小时时增加了体外存活的GalC+少突胶质细胞数量。用干扰素-γ（IFN-γ）激活的小胶质细胞条件培养基未观察到这些效应。未激活的小胶质细胞条件培养基与OPC中核因子κB结合（NF-κB）p65亚基的上调有关。使用针对κB抑制因子（IκB）的反义寡核苷酸可诱导OPC中p65亚基活化，并且与未激活的小胶质细胞条件培养基一样，也能抑制OPC凋亡并促进细胞成熟。抗血小板衍生生长因子（PDGF）抗体消除了这种效应，尽管PDGF-A链在未激活和IFN-γ激活的小胶质细胞中表达水平相似，且两种条件培养基中PDGF-A链的生物活性水平也相似。然而，只有未激活的小胶质细胞条件培养基能将磷脂酰-3-肌醇（PI-3）激酶募集到PDGF-α受体，并与内源性PDGF-A链协同作用以增加NF-κB活化。这些结果表明，小胶质细胞根据其激活状态产生可溶性因子，通过影响PDGF-α受体信号通路促进少突胶质细胞发育。
