Altered Regulation of CD200 Receptor in Monocyte-Derived Macrophages from Individuals with Parkinson's Disease
Altered Regulation of CD200 Receptor in Monocyte-Derived Macrophages from Individuals with Parkinson's Disease
复制标题
帕金森病患者单核细胞来源的巨噬细胞中 CD200 受体的调节发生改变
DOI：
10.1007/s11064-009-0094-6
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发表时间：
2010-04-01
影响因子：
4.4
通讯作者：
Ding, Jian-Qing
中科院分区：
文献类型：
--
作者：
Luo, Xiao-Guang;Zhang, Ji-Juan;Ding, Jian-Qing
小胶质细胞是脑内具有代表性的髓系细胞，其过度活化在帕金森病（PD）的发病机制中起重要作用。小胶质细胞的活化被认为是由CD 200-CD 200 R信号转导调节的。单核细胞源性巨噬细胞（MDM）作为小胶质细胞的外周对应物，具有相同的祖细胞和抗原标志物，具有相似的生物学行为，并反映了脑中小胶质细胞的功能。在这里，我们研究了CD 200 R的表达和它的调节MDM从32例PD，27个年龄匹配的老年对照，28个年轻的对照。我们发现年轻对照组、老年对照组和PD患者的MDM中基础CD 200 R表达相似。然而，在各种条件下，在老年组中，特别是在PD患者中，MDM中诱导CD 200 R表达受损。与年龄匹配的对照组相比，PD病例的MDM中与垂死的PC 12细胞共培养诱导的CD 200 R表达选择性降低。我们还发现诱导型CD 200 R表达与PD的发病年龄和MDM释放的肿瘤坏死因子-α（TNF-α）呈负相关。这些结果表明，在衰老过程中，特别是在PD中，MDM中的CD 200-CD 200 R信号传导存在内在异常。我们推测，在PD大脑中，小胶质细胞可能会发生类似于MDM的异常。
Microglia are the representative myeloid cells in the brain, and their over-activation plays an important role in the pathogenesis of Parkinson's disease (PD). Microglia activation is believed to be regulated by the CD200-CD200R signaling. As the peripheral counterpart of microglia, monocyte-derived macrophages (MDMs) share the same progenitor and antigen markers, and they have similar biological behaviors and mirror microglial function in the brain. Here, we studied CD200R expression and its regulation in MDMs from 32 PD cases, 27 age-matched old controls, and 28 young controls. We found that the basal CD200R expression is similar in MDMs from young control, old control and PD patients. However, the induction of CD200R expression in MDMs under various conditions is impaired in the old groups, especially in PD patients. There was a selective decrease in CD200R expression induced by co-culture with dying PC12 cells in MDMs from PD cases, as compared with MDMs from the age-matched controls. We also found that the inducible CD200R expression correlated inversely with the onset age of PD and to tumor necrosis factor-alpha (TNF-alpha) released from MDMs. These results suggest an intrinsic abnormality in the CD200-CD200R signaling in MDMs during aging and, especially, in PD. We speculate that in the PD brain, microglia might undergo abnormalities similar to MDMs.