Piddlesden S, Lassmann H, Laffafian I, Morgan B P, Linington C
Department of Medicine, University of Wales College of Medicine, Cardiff, Wales, U.K.
Clin Exp Immunol. 1991 Feb;83(2):245-50. doi: 10.1111/j.1365-2249.1991.tb05622.x.
The effects of decomplementation by cobra venom factor (CVF) on the pathogenesis of inflammation and demyelination in experimental allergic encephalomyelitis (EAE) and acute antibody-mediated demyelinating EAE (ADEAE) have been quantified histologically and immunocytochemically. In rats immunized with 50 micrograms of myelin basic protein in Freund's complete adjuvant containing 100 micrograms heat-killed Mycobacterium tuberculosis H37Ra, clinical signs of EAE were completely suppressed by two injections of CVF given 9 and 12 days post-immunization. Suppression of clinical disease was associated with a dramatic reduction in peri-vascular inflammation in the CNS, although immunohistochemical staining identified small numbers of infiltrating T cells and macrophages. In contrast, CVF treatment had no significant effect on the clinical severity of ADEAE and although C9 deposition within the CNS was virtually abolished, there was no statistically significant decrease in the extent of demyelination or inflammation. These observations indicate that in the absence of complement components C3 and C5 an antibody-dependent cell-mediated cytotoxic response plays an important role in the pathogenesis of antibody-mediated demyelination. The major role of the complement cascade in EAE appears to be the generation of pro-inflammatory factors that enhance the inflammatory response within the CNS in animals facing a mild encephalitogenic challenge.
通过眼镜蛇毒因子（CVF）进行补体灭活对实验性变态反应性脑脊髓炎（EAE）和急性抗体介导的脱髓鞘性EAE（ADEAE）炎症和脱髓鞘发病机制的影响，已通过组织学和免疫细胞化学方法进行了定量研究。在用含有100微克热灭活结核分枝杆菌H37Ra的弗氏完全佐剂免疫50微克髓鞘碱性蛋白的大鼠中，在免疫后第9天和第12天给予两次CVF注射，可完全抑制EAE的临床症状。临床疾病的抑制与中枢神经系统血管周围炎症的显著减少相关，尽管免疫组织化学染色发现有少量浸润的T细胞和巨噬细胞。相比之下，CVF治疗对ADEAE的临床严重程度没有显著影响，尽管中枢神经系统内C9沉积几乎完全消除，但脱髓鞘或炎症程度在统计学上没有显著降低。这些观察结果表明，在缺乏补体成分C3和C5的情况下，抗体依赖性细胞介导的细胞毒性反应在抗体介导的脱髓鞘发病机制中起重要作用。补体级联反应在EAE中的主要作用似乎是产生促炎因子，在面临轻度致脑炎性挑战的动物中增强中枢神经系统内的炎症反应。
