Department of Anatomy, Brain Research Institute, Chungnam National University School of Medicine, Daejeon, South Korea.
Brain Res. 2012 Oct 24;1481:90-6. doi: 10.1016/j.brainres.2012.08.053. Epub 2012 Sep 4.
CD200 is a glycoprotein that is expressed on the surfaces of neurons and other cells. It interacts with its receptor, CD200R, which is expressed on cells of the myeloid lineage, including microglia. The interaction of CD200 with its receptor plays a significant role in maintaining microglia in a quiescent state; thus, a decrease in CD200 expression in the brain is associated with evidence of microglial activation. However, their roles in pathological progression remain unclear. We examined the expression of CD200 in kainic acid (KA)-induced neurodegeneration of the mouse hippocampus. Our quantitative analysis revealed that CD200 was constitutively expressed in the normal brain and transiently upregulated by KA treatment. At the cellular level, CD200 was expressed in neurons in control, and was upregulated primarily in the microglia of KA-treated mouse hippocampi. We examined the contribution of CD200 to both the classical and alternative activation of microglia in vitro using an adult microglia culture, which was exposed to interleukin-4 (IL-4) with and without lipopolysaccharide (LPS). CD200 expression was increased after exposure to IL-4, but not to LPS. These in vivo experiments demonstrated that CD200 was transiently expressed in microglia in a process mediated by the inflammatory response. Based on CD200R expression in microglia, it suggests that microglia is maintained in an activated state with autocrine signaling by interactions between microglial CD200 and its CD200R. Moreover, we suggest that CD200 may be expressed in the alternative activation of microglia and play a beneficial role in neuroinflammation.
CD200 是一种糖蛋白，表达于神经元和其他细胞表面。它与表达于髓系细胞（包括小胶质细胞）表面的受体 CD200R 相互作用。CD200 与其受体的相互作用在维持小胶质细胞静息状态中发挥重要作用；因此，大脑中 CD200 表达的减少与小胶质细胞激活的证据有关。然而，其在病理进展中的作用仍不清楚。我们研究了 CD200 在鼠海马区红藻氨酸（KA）诱导的神经退行性变中的表达。我们的定量分析显示，CD200 在正常脑中持续表达，并被 KA 处理短暂上调。在细胞水平上，CD200 在对照中的神经元中表达，并在 KA 处理的鼠海马中的小胶质细胞中主要上调。我们使用成年小胶质细胞培养物，在体外研究了 CD200 对小胶质细胞经典激活和替代激活的贡献，该培养物暴露于白细胞介素-4（IL-4）和脂多糖（LPS）。CD200 在暴露于 IL-4 后表达增加，但在 LPS 后没有增加。这些体内实验表明，CD200 在炎症反应介导的过程中在小胶质细胞中短暂表达。基于小胶质细胞中 CD200R 的表达，表明小胶质细胞通过小胶质细胞 CD200 与其 CD200R 之间的相互作用，维持在激活状态下，具有自分泌信号。此外，我们认为 CD200 可能在小胶质细胞的替代激活中表达，并在神经炎症中发挥有益作用。
