Dyer C A, Benjamins J A
Department of Neurology, Wayne State University, School of Medicine, Detroit, MI 48201.
J Neurosci Res. 1991 Dec;30(4):699-711. doi: 10.1002/jnr.490300414.
Galactocerebroside (GalC) and sulfated galactocerebroside (sulfatide) are sphingolipids highly enriched in myelin. The binding of antibodies reactive with either sulfatide or GalC to cultured oligodendrocytes causes a Ca2+ influx, followed by microtubule depolymerization; however, antisulfatide is less effective than anti-GalC in altering cytoskeleton. Typical Ca2+ responses are delayed for both antibodies but are transient for sulfatide-reactive antibodies in contrast to the sustained responses previously reported for anti-GalC (Dyer and Benjamins, J Cell Biol 111: 625-633, 1990). Approximately one-half as many oligodendrocytes respond to sulfatide-reactive antibodies (about 39%) as to anti-GalC (about 75%). Subpopulations of oligodendrocytes were identified that responded to neither antibody, only one antibody, or both antibodies, indicating that sulfatide and GalC independently mediate Ca2+ responses. These results suggest that sulfatide and GalC have different physiologic roles in regulating elaboration of myelin membrane by oligodendrocytes in vivo and support the possibility that viral or immune attack via GalC or sulfatide on oligodendrocytes may mimic normal signals in a manner that disrupts the sequence of events that coordinates myelination or maintenance of myelin in vivo.
半乳糖脑苷脂(GalC)和硫酸化半乳糖脑苷脂(硫脂)是高度富集于髓鞘中的鞘脂。与硫脂或GalC反应的抗体与培养的少突胶质细胞结合会导致Ca2+内流,随后微管解聚;然而,抗硫脂抗体在改变细胞骨架方面比抗GalC抗体效果差。两种抗体的典型Ca2+反应均有延迟,但硫脂反应性抗体的反应是短暂的,这与先前报道的抗GalC抗体的持续反应形成对比(戴尔和本杰明斯,《细胞生物学杂志》111: 625 - 633, 1990)。对硫脂反应性抗体产生反应的少突胶质细胞数量约为对抗GalC抗体产生反应的少突胶质细胞数量的一半(约39%对约75%)。已鉴定出少突胶质细胞亚群,它们对两种抗体均无反应、仅对一种抗体有反应或对两种抗体都有反应,这表明硫脂和GalC独立介导Ca2+反应。这些结果表明,硫脂和GalC在体内调节少突胶质细胞髓鞘膜的形成方面具有不同的生理作用,并支持这样一种可能性,即通过GalC或硫脂对少突胶质细胞进行病毒或免疫攻击可能以一种破坏体内协调髓鞘形成或髓鞘维持的事件序列的方式模拟正常信号。