Hendriks Jerome J A, Teunissen Charlotte E, de Vries Helga E, Dijkstra Christine D
Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
Brain Res Brain Res Rev. 2005 Apr;48(2):185-95. doi: 10.1016/j.brainresrev.2004.12.008.
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Demyelination is a classical feature of MS lesions, and neurological deficits are often ascribed to the reduced signal conduction by demyelinated axons. However, recent studies emphasize that axonal loss is an important factor in MS pathogenesis and disease progression. Axonal loss is found in association with cellular infiltrates in MS lesions. In this review, we discuss the possible contribution of the innate immune system in this process. In particular, we describe how infiltrated macrophages may contribute to axonal loss in MS and in experimental autoimmune encephalomyelitis (EAE), the animal model for MS. An overview is given of the possible effects of mediators, which are produced by activated macrophages, such as such as pro-inflammatory cytokines, free radicals, glutamate and metalloproteases, on axonal integrity. We conclude that infiltrated macrophages, which are activated to produce pro-inflammatory mediators, may be interesting targets for therapeutic approaches aimed to prevent or reduce axonal loss during exacerbation of inflammation. Interference with the process of infiltration and migration of monocytes across the blood-brain barrier is one of the possibilities to reduce the damage by activated macrophages.
多发性硬化症（MS）是一种中枢神经系统（CNS）的慢性炎性脱髓鞘疾病。脱髓鞘是MS病灶的一个典型特征，神经功能缺损常归因于脱髓鞘轴突信号传导的降低。然而，最近的研究强调轴突丢失是MS发病机制和疾病进展中的一个重要因素。在MS病灶中发现轴突丢失与细胞浸润有关。在这篇综述中，我们讨论了固有免疫系统在这个过程中可能发挥的作用。特别是，我们描述了浸润的巨噬细胞如何在MS以及实验性自身免疫性脑脊髓炎（EAE，MS的动物模型）中导致轴突丢失。概述了活化巨噬细胞产生的介质，如促炎细胞因子、自由基、谷氨酸和金属蛋白酶，对轴突完整性可能产生的影响。我们得出结论，被激活以产生促炎介质的浸润巨噬细胞，可能是旨在预防或减少炎症加重期间轴突丢失的治疗方法的有趣靶点。干扰单核细胞穿过血脑屏障的浸润和迁移过程是减少活化巨噬细胞造成损伤的一种可能性。
