Expression of chemokine receptors CCR1 and CCR5 reflects differential activation of mononuclear phagocytes in pattern II and pattern III multiple sclerosis lesions
Expression of chemokine receptors CCR1 and CCR5 reflects differential activation of mononuclear phagocytes in pattern II and pattern III multiple sclerosis lesions
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DOI：
10.1093/jnen/63.3.262
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发表时间：
2004-03-01
影响因子：
3.2
通讯作者：
Ransohoff, RM
中科院分区：
文献类型：
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作者：
Mahad, DJ;Trebst, C;Ransohoff, RM
多发性硬化症（MS）是一种中枢神经系统炎症性脱髓鞘疾病。最近的一项研究确定了活动性MS病变中的4种脱髓鞘模式。II型病变的特征表明髓鞘损伤的主要炎症机制，而III型病变显示出与退变性少突胶质细胞病一致的特征。单核吞噬细胞的募集、分化和活化依赖于趋化因子受体的表达。使用免疫组化，我们定量的CCR 1和CCR 5的细胞表达的模式II（n = 21）和模式III（n = 17）的不同脱髓鞘活性的病变区域。两种病变模式中的浸润单核细胞共表达CCR1和CCR5，表明单核细胞募集到CNS中的保守机制。在II型病变中，与早期活动性脱髓鞘区域相比，晚期活动性脱髓鞘区域表达CCR1的细胞数量显著减少，而CCR5增加。与此形成鲜明对比的是，在III型病变的所有区域中，表达CCR1和CCR5的细胞数量相等。由于缺氧样机制可能在III型病变中起作用，我们将这些研究扩展到白色梗死（n = 7），其中CCR 1的表达更像III型病变而不是II型病变。根据单核吞噬细胞趋化因子受体表达判断，I型和III型MS病变中似乎存在不同的组织环境。
Multiple sclerosis (MS) is an inflammatory demyelinating disorder of the CNS. A recent study identified 4 patterns of demyelination in active MS lesions. The characteristics of pattern II lesions suggested a primary inflammatory mechanism of myelin injury, while pattern III lesions showed features consistent with dying-back oligodendrogliopathy. The recruitment, differentiation, and activation of mononuclear phagocytes are dependent on the expression of chemokine receptors. Using immunohistochernistry we quantified cellular expression of CCR1 and CCR5 in pattern II (n = 21) and pattern III (n = 17) lesion areas of differing demyelinating activity. Infiltrating monocytes in both lesion patterns co-expressed CCR1 and CCR5, suggesting conserved mechanisms of monocyte recruitment into the CNS. In pattern II lesions, the number of cells expressing CCR1 significantly decreased while CCR5 increased in late active compared with early active demyelinating regions. In striking contrast, numbers of cells expressing CCR1 and CCR5 were equal in all regions of pattern III lesions. As hypoxialike mechanisms may play a role in pattern III lesions, we extended these studies to white matter infarcts (n = 7) in which the expression of CCR1 better resembled pattern III than pattern II lesions. As judged by mononuclear phagocyte chemokine receptor expression, there appear to be distinct tissue environments in pattern I and III MS lesions.