Reiman Rachael, Campos Torres Antonio, Martin Brian K, Ting Jenny P, Campbell Iain L, Barnum Scott R
Department of Microbiology, University of Alabama at Birmingham, 845 19th St. S., Birmingham, AL 35294, USA.
Neurosci Lett. 2005 Dec 30;390(3):134-8. doi: 10.1016/j.neulet.2005.08.022. Epub 2005 Sep 9.
Complement is implicated in the pathology of neurodegenerative and inflammatory disease in the central nervous system (CNS). Although studies demonstrate that inhibition of complement activation attenuates disease development in the CNS, the specific complement components that contribute to the pathogenesis of CNS diseases remain unclear. To dissect the role of C5a in CNS disease, we developed a transgenic mouse that produces C5a exclusively in the brain using the astrocyte-specific, murine glial fibrillary acidic protein (GFAP) promoter. C5a/GFAP mice develop normally and do not demonstrate any signs of spontaneous inflammation or neurodegeneration with age. Using C5a/GFAP mice, we examined the outcome of the animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). To our surprise the onset and severity of myelin oligodendrocyte glycoprotein-induced EAE was essentially identical between C5a/GFAP and control mice. These results demonstrate that C5a, despite it is pro-inflammatory functions, is not critical to the development and progression of EAE.
补体与中枢神经系统（CNS）的神经退行性疾病和炎症性疾病的病理过程有关。尽管研究表明抑制补体激活可减轻中枢神经系统疾病的发展，但导致中枢神经系统疾病发病机制的特定补体成分仍不清楚。为了剖析C5a在中枢神经系统疾病中的作用，我们构建了一种转基因小鼠，该小鼠使用星形胶质细胞特异性的小鼠胶质纤维酸性蛋白（GFAP）启动子在脑内特异性产生C5a。C5a/GFAP小鼠发育正常，不会随着年龄增长出现任何自发性炎症或神经退行性变的迹象。利用C5a/GFAP小鼠，我们研究了多发性硬化症动物模型——实验性自身免疫性脑脊髓炎（EAE）的结果。令我们惊讶的是，C5a/GFAP小鼠和对照小鼠之间，髓鞘少突胶质细胞糖蛋白诱导的EAE的发病和严重程度基本相同。这些结果表明，尽管C5a具有促炎功能，但对EAE的发生和发展并不关键。
