Kerlero de Rosbo N, Honegger P, Lassmann H, Matthieu J M
Laboratoire de Neurochimie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
J Neurochem. 1990 Aug;55(2):583-7. doi: 10.1111/j.1471-4159.1990.tb04173.x.
A monoclonal antibody (8-18C5) directed against myelin/oligodendrocyte glycoprotein (MOG) induced demyelination in aggregating brain cell cultures. With increasing doses of anti-MOG antibody in the presence of complement, myelin basic protein (MBP) concentration decreased in a dose-related manner. A similar, albeit less pronounced, effect was observed on specific activity of 2',3'-cyclic nucleotide 3'-phosphohydrolase. In the absence of complement, anti-MOG antibody did not induce detectable demyelination. In contrast to the effect of anti-MOG antibody and as expected, anti-MBP antibody did not demyelinate aggregating brain cell cultures in the presence of complement. These results provide additional support to the suggestion that MOG, a quantitatively minor myelin component located on the external side of the myelin membrane, is a good target antigen for antibody-induced demyelination. Indeed, they show that a purified anti-MOG antibody directed against a single epitope on the glycoprotein can produce demyelination, not only in vivo as previously shown, but also in cultures. Such an observation has not been made with polyclonal antisera raised against purified myelin proteins like MBP and proteolipid protein, the major protein components of the myelin membrane, or myelin-associated glycoprotein. These observations may have important implications regarding the possible role of anti-MOG antibodies in demyelinating diseases.
一种针对髓鞘/少突胶质细胞糖蛋白（MOG）的单克隆抗体（8-18C5）在聚集的脑细胞培养物中诱导了脱髓鞘。在补体存在的情况下，随着抗MOG抗体剂量的增加，髓鞘碱性蛋白（MBP）浓度呈剂量相关下降。对2',3'-环核苷酸3'-磷酸水解酶的比活性也观察到了类似但不太明显的效应。在没有补体的情况下，抗MOG抗体未诱导出可检测到的脱髓鞘。与抗MOG抗体的效应相反且如预期的那样，抗MBP抗体在补体存在时并未使聚集的脑细胞培养物发生脱髓鞘。这些结果为以下观点提供了额外支持：MOG是位于髓鞘膜外侧的一种数量较少的髓鞘成分，是抗体诱导脱髓鞘的良好靶抗原。实际上，它们表明针对糖蛋白上单个表位的纯化抗MOG抗体不仅如先前所示在体内可产生脱髓鞘，在培养物中也可产生脱髓鞘。针对髓鞘膜的主要蛋白质成分如MBP、蛋白脂质蛋白或髓鞘相关糖蛋白等纯化髓鞘蛋白产生的多克隆抗血清尚未有这样的观察结果。这些观察结果可能对抗MOG抗体在脱髓鞘疾病中可能的作用具有重要意义。
