Deficiency of the complement regulator CD59a enhances disease severity, demyelination and axonal injury in murine acute experimental allergic encephalomyelitis
Deficiency of the complement regulator CD59a enhances disease severity, demyelination and axonal injury in murine acute experimental allergic encephalomyelitis
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DOI：
10.1038/labinvest.3700015
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发表时间：
2004-01-01
影响因子：
5
通讯作者：
Morgan, BP
中科院分区：
文献类型：
--
作者：
Mead, RJ;Neal, JW;Morgan, BP
越来越多的证据表明补体，特别是终末途径（膜攻击复合物; MAC）在多发性硬化和实验性过敏性脑脊髓炎中诱导脱髓鞘。在本文中，我们研究了疾病的过程和病理变化，在小鼠缺乏MAC组件的主要调节，CD 59 a，在急性实验性变态反应性脑脊髓炎的过程中诱导的免疫与重组髓鞘少突胶质细胞糖蛋白。在CD 59 a缺陷小鼠中，疾病发病率和严重程度显著增加。在来自CD 59 a缺陷小鼠和对照小鼠的脊髓横截面中评估炎症、脱髓鞘和轴突损伤的程度，并且所有这些参数在不存在CD 59 a的情况下增强。CD 59 a缺陷小鼠的髓鞘丢失和轴突损伤区域与MAC的沉积相关，坚定地暗示MAC是观察到的损伤的原因。这些发现与某些类型的人类脱髓鞘相关，其中发现与病理学相关的MAC的大量沉积。
There is a growing body of evidence implicating complement and, in particular, the terminal pathway ( membrane attack complex; MAC) in inducing demyelination in multiple sclerosis and experimental allergic encephalomyelitis. In this paper, we examined the disease course and pathological changes in mice deficient in the major regulator of MAC assembly, CD59a, during the course of acute experimental allergic encephalomyelitis induced by immunisation with recombinant myelin oligodendrocyte glycoprotein. Disease incidence and severity were significantly increased in CD59a-deficient mice. The extent of inflammation, demyelination and axonal injury were assessed in spinal cord cross-sections from CD59a- deficient and control mice, and all these parameters were enhanced in the absence of CD59a. Areas of myelin loss and axonal damage in CD59a-deficient mice were associated with deposits of MAC, firmly implicating MAC as a cause of the observed injury. These findings are relevant to some types of human demyelination, where abundant deposits of MAC are found in association with pathology.