THE ROLE OF COMPLEMENT IN THE PATHOGENESIS OF EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS
THE ROLE OF COMPLEMENT IN THE PATHOGENESIS OF EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS
复制标题
DOI：
10.1093/brain/112.4.895
复制
发表时间：
1989-08-01
期刊：
影响因子：
14.5
通讯作者：
COMPSTON, DAS
中科院分区：
文献类型：
--
作者：
LININGTON, C;MORGAN, BP;COMPSTON, DAS
在Lewis大鼠急性实验性变态反应性脑脊髓炎(EAE)的协同模型中，研究了补体在脱髓鞘和炎症发病机制中的作用。用眼镜蛇毒因子耗尽血清补体可抑制50ug豚鼠碱性蛋白弗氏完全佐剂免疫或被动转移107诱导的急性炎症性EAE的临床表达，但不能抑制5倍。107 MBP活化的脾细胞。尽管主动诱导的EAE抑制了临床疾病，但CVF仅在早期(免疫后12天)炎症灶减少35%的情况下才对中枢神经系统炎症的严重程度有显著影响。三天后，这种差异已经消失，在中枢神经系统炎症的严重程度上没有检测到显著差异，尽管对照组动物表现出严重的疾病，CVF组临床正常。在这些模型中，脱髓鞘是通过全身注射抗髓鞘少突胶质细胞糖蛋白(MOG)单抗8-18C5开始的，该单抗在体外以剂量、FC和补体依赖的方式裂解少突胶质细胞，并在体内诱导EAE大鼠中枢神经系统脱髓鞘。用CVF处理可降低该抗体在体内启动脱髓鞘的能力，而且其F(Ab)2‘’片段对EAE的临床病程没有影响，也不能启动正常动物的脱髓鞘。因此，补体依赖机制既参与急性炎症性病变的临床表达，也参与抗体介导的EAE脱髓鞘的发病机制。
The role of complement in the pathogenesis of demyelination and inflammation has been investigated in a synergistic model of acute experimental allergic encephalomyelitis (EAE) in the Lewis rat. Depletion of serum complement with cobra venom factor (CVF) suppressed the clinical expression of acute inflammatory EAE induced either by immunization with 50 .mu.g guinea pig basic protein (MBP) in Freund''s complete adjuvant, or by the passive transfer of 107, but not 5 .times. 107 MBP activated spleen cells. Despite the suppression of clinical disease in actively induced EAE, treatment with CVF only had a significant effect on the severity of CNS inflammation in early disease (12 days postimmunization) when the number of inflammatory foci was reduced by 35%. Three days later this difference had resolved and no significant difference could be detected in the severity of CNS inflammation, although control animals exhibited severe disease, the CVF treated group being clinically normal. Demyelination in these models is initiated by systemic injection of the antimyelin oligodendrocyte glycoprotein (MOG) monoclonal antibody, 8-18C5, which in vitro lyses oligodendrocytes in a dose, Fc and complement-dependent manner and in vivo induces extensive CNS demyelination in rats with EAE. Treatment with CVF reduced the ability of this antibody to initiate demyelination in vivo and furthermore, its F(ab)2'' fragment had no effect on the clinical course of EAE and was unable to initiate demyelination in normal animals. Complement-dependent mechanisms are therefore involved both in the clinical expression of acute inflammatory lesions and in the pathogenesis of antibody-mediated demyelination in EAE.