Ruuls S R, Van Der Linden S, Sontrop K, Huitinga I, Dijkstra C D
Department of Cell Biology and Immunology, Faculty of Medicine, Vrije Universiteit, Amsterdam, The Netherlands.
Clin Exp Immunol. 1996 Mar;103(3):467-74. doi: 10.1111/j.1365-2249.1996.tb08304.x.
Macrophages constitute a large proportion of the inflammatory cells that infiltrate the central nervous system (CNS) of animals with EAE. Through the production of inflammatory mediators these infiltrating macrophages can contribute to the regulation of the immune reaction within the CNS, that eventually results in neurological deficits associated with EAE. NO, a free radical produced by macrophages and other cell types, has been put forward as such an immune mediator. In the present study we show that macrophages isolated from the CNS of Lewis rats with clinical signs of EAE produce elevated amounts of NO. We treated rats, in which EAE was induced, with N(omega) -nitro-L-arginine-methylester or N(g)-monomethyl-L-arginine, inhibitors of NO synthase, either systemically via intraperitoneal injection, or intracerebrally via a cannula placed in the lateral ventricle. Both treatments resulted in a marked aggravation of clinical signs of EAE. These data point to an important role of NO, produced by infiltrating macrophages, as an immune-suppressor in the disease process during EAE.
巨噬细胞在患有实验性自身免疫性脑脊髓炎（EAE）的动物中枢神经系统（CNS）中浸润的炎性细胞中占很大比例。通过产生炎性介质，这些浸润的巨噬细胞可有助于调节中枢神经系统内的免疫反应，最终导致与EAE相关的神经功能缺损。一氧化氮（NO）是巨噬细胞和其他细胞类型产生的一种自由基，已被提出作为这样一种免疫介质。在本研究中，我们表明从患有EAE临床症状的Lewis大鼠中枢神经系统中分离出的巨噬细胞产生的NO量升高。我们用N（ω）-硝基-L-精氨酸甲酯或N（g）-单甲基-L-精氨酸（NO合酶抑制剂）治疗诱导了EAE的大鼠，要么通过腹腔注射全身给药，要么通过置于侧脑室的套管脑内给药。两种治疗均导致EAE临床症状明显加重。这些数据表明，浸润的巨噬细胞产生的NO作为EAE疾病过程中的一种免疫抑制剂具有重要作用。
