Banerjee Debatri, Dick Andrew D
Department of Ophthalmology, University of Bristol, UK.
Ocul Immunol Inflamm. 2004 Jun;12(2):115-25. doi: 10.1080/09273940490895326.
Tissue expression of CD200 generates inhibitory or down-regulatory signals to macrophages and microglia within CNS and retina. Our interests were to investigate whether blocking CD200 receptor (CD200R) signalling in vivo results in macrophage activation and thus aggravation of EAU in Lewis rats.
Retinal extract-immunised Lewis rats were treated day 3 and 5 post-immunisation with CD200R mAb or normal mouse serum. Phenotypic analysis of the leucocyte infiltrate and disease severity was clinically and histogically examined.
Rats administered with CD200R mAb developed earlier onset of EAU and more severe disease. Blocking CD200R increased retinal neuronal CD200 expression and, although disease severity was increased concomitant with an increase in NOS-2 expression, retinal macrophage numbers were not increased.
Contemporaneous with data from CD200KO mice, these results support the notion that CD200-CD200R signalling suppresses macrophage activation. Exacerbation of EAU in both CD200KO mice and Lewis rats when CD200-CD200R interaction is blocked suggests that this could be an avenue for therapeutic intervention.
CD200的组织表达可对中枢神经系统和视网膜内的巨噬细胞和小胶质细胞产生抑制或下调信号。我们感兴趣的是研究在体内阻断CD200受体（CD200R）信号传导是否会导致巨噬细胞活化，从而加重Lewis大鼠的实验性自身免疫性葡萄膜炎（EAU）。
用视网膜提取物免疫的Lewis大鼠在免疫后第3天和第5天用CD200R单克隆抗体或正常小鼠血清进行治疗。通过临床和组织学检查对白细胞浸润的表型分析和疾病严重程度进行评估。
给予CD200R单克隆抗体的大鼠EAU发病更早且病情更严重。阻断CD200R可增加视网膜神经元CD200的表达，尽管疾病严重程度随着一氧化氮合酶2（NOS-2）表达的增加而增加，但视网膜巨噬细胞数量并未增加。
与来自CD200基因敲除小鼠的数据一致，这些结果支持CD200-CD200R信号传导抑制巨噬细胞活化的观点。当CD200-CD200R相互作用被阻断时，CD200基因敲除小鼠和Lewis大鼠的EAU病情加重，这表明这可能是一个治疗干预的途径。
