Ruuls S R, Bauer J, Sontrop K, Huitinga I, 't Hart B A, Dijkstra C D
Department of Cell Biology and Immunology, Faculty of Medicine, Vrije Universiteit, Amsterdam, Netherlands.
J Neuroimmunol. 1995 Feb;56(2):207-17. doi: 10.1016/0165-5728(94)00154-g.
During experimental allergic encephalomyelitis (EAE), both blood-borne macrophages as well as activated, resident microglial cells are considered to be involved in inflammatory reactions in the central nervous system (CNS), resulting in the neurological deficits common to EAE. Both cell types can produce multiple mediators of tissue damage, among which are the reactive oxygen species (ROS). In this study we show that macrophages and microglial cells, isolated from the CNS of Lewis rats with clinical signs of EAE, exhibited significantly elevated spontaneous and phorbol myristate acetate (PMA)-inducible levels of ROS compared to similar cells isolated from healthy controls, sham (complete Freund's adjuvant, CFA)-immunized rats as well as rats sacrificed before the manifestation of clinical signs of EAE. However, during clinical EAE, peripheral blood mononuclear cells (PBMC) did not show increased spontaneous nor PMA-inducible ROS production compared to controls. In vivo treatment of EAE with catalase, which scavenges the ROS H2O2, markedly suppressed the severity of the disease as compared to sham (albumin)-treated controls. In contrast, superoxide dismutase had no effect on clinical signs. Our studies point at a putative functional role for ROS, and in particular H2O2, in the pathogenesis of EAE.
在实验性自身免疫性脑脊髓炎（EAE）期间，血源性巨噬细胞以及活化的常驻小胶质细胞都被认为参与了中枢神经系统（CNS）的炎症反应，导致了EAE常见的神经功能缺损。这两种细胞类型都能产生多种组织损伤介质，其中包括活性氧（ROS）。在本研究中，我们发现，与从健康对照、用弗氏完全佐剂（CFA）免疫的假手术大鼠以及在EAE临床症状出现前处死的大鼠中分离出的类似细胞相比，从出现EAE临床症状的Lewis大鼠中枢神经系统中分离出的巨噬细胞和小胶质细胞表现出显著升高的自发和佛波酯（PMA）诱导的ROS水平。然而，在临床EAE期间，与对照组相比，外周血单核细胞（PBMC）的自发和PMA诱导的ROS产生并未增加。用能清除ROS过氧化氢（H2O2）的过氧化氢酶对EAE进行体内治疗，与假手术（白蛋白）治疗的对照组相比，显著抑制了疾病的严重程度。相反，超氧化物歧化酶对临床症状没有影响。我们的研究指出了ROS，特别是H2O2在EAE发病机制中的假定功能作用。
