Meuth Sven G, Simon Ole J, Grimm Alexander, Melzer Nico, Herrmann Alexander M, Spitzer Philipp, Landgraf Peter, Wiendl Heinz
University of Wuerzburg, Department of Neurology, Josef-Schneider-Strasse 11, 97080 Wuerzburg, Germany.
J Neuroimmunol. 2008 Feb;194(1-2):62-9. doi: 10.1016/j.jneuroim.2007.11.013.
Multiple sclerosis is a chronic disabling CNS disorder, characterized by autoimmune inflammatory demyelination and neurodegeneration. CD200, broadly expressed on neurons and endothelial cells, mediates inhibitory signals through its receptor, CD200R, on cells of myeloid origin. Antibody-mediated blockade of CD200R leads to an aggravated clinical course of rodent experimental autoimmune encephalomyelitis in vivo, accompanied by profoundly augmented cellular infiltrates consisting of T cells and activated iNOS(+) macrophages in inflammatory spinal cord lesions. In vitro blockade of CD200R on macrophages leads to enhanced IFN-gamma-induced release of IL6 and neuronal cell death in co-cultures with hippocampal neurons expressing CD200. CD200 and its receptor could also be detected on neurons and macrophages in human MS plaques. Therefore the CD200-CD200R pathway seems of critical relevance for macrophage-mediated damage in autoimmune inflammation of the CNS.
多发性硬化症是一种慢性致残性中枢神经系统疾病，其特征为自身免疫性炎性脱髓鞘和神经退行性变。CD200广泛表达于神经元和内皮细胞上，通过其受体CD200R在髓系来源的细胞上介导抑制性信号。抗体介导的CD200R阻断会导致啮齿动物实验性自身免疫性脑脊髓炎在体内的临床病程加重，同时伴有炎性脊髓损伤中由T细胞和活化的诱导型一氧化氮合酶（iNOS）阳性巨噬细胞组成的细胞浸润显著增加。体外阻断巨噬细胞上的CD200R会导致在与表达CD200的海马神经元共培养时，γ干扰素诱导的白细胞介素6释放增加以及神经元细胞死亡。在人类多发性硬化症斑块中的神经元和巨噬细胞上也能检测到CD200及其受体。因此，CD200-CD200R通路似乎与中枢神经系统自身免疫性炎症中巨噬细胞介导的损伤密切相关。
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