Monocytes, microglia and CD200-CD200R1 signaling are essential in the transmission of inflammation from the periphery to the central nervous system.
Monocytes, microglia and CD200-CD200R1 signaling are essential in the transmission of inflammation from the periphery to the central nervous system.
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单核细胞、小胶质细胞和 CD200-CD200R1 信号传导对于炎症从外周到中枢神经系统的传递至关重要。
DOI：
10.1111/jnc.13972
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Ren Yan
中科院分区：
文献类型：
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作者：
Xie Xin;Luo Xiaoguang;Liu Na;Li Xiaohong;Lou Fan;Zheng Yumin;Ren Yan
已知外周炎症会引发神经炎症和神经退行性疾病。然而，炎症从外周向中枢神经系统（CNS）传播过程中的关键成分仍不清楚。将脂多糖（LPS）给予Sprague-Dawley大鼠以诱导外周炎症。静脉注射和黑质内注射氯膦酸盐脂质体，分别消耗单核细胞和小胶质细胞。将重组CD 200融合蛋白（CD 200 Fc）或抗CD 200 R1抗体注射到黑质中，以操纵CD 200和CD 200 R1的参与。免疫组织化学和免疫荧光染色用于测量小胶质细胞活化和多巴胺能神经元损失。脑促炎细胞因子的表达（即，肿瘤坏死因子α，IL-1β）和CD 200-CD 200 R1信号转导。我们的数据显示，外周LPS注射激活了小胶质细胞并诱导了促炎细胞因子水平的增加（即，肿瘤坏死因子α，IL-1β）。单核细胞或小胶质细胞的耗竭抑制了由外周LPS给药诱导的这些炎症作用。外周注射LPS后黑质CD 200和CD 200 R1表达增加。外周LPS注射诱导的多巴胺能神经元损失通过用抗CD 200 R1抗体阻断CD 200-CD 200 R1信号传导而加速，并通过用CD 200 Fc增强信号传导而减弱。这些结果强调了单核细胞、小胶质细胞和CD 200-CD 200 R1信号在炎症从外周向CNS传播中的重要性。
Peripheral inflammation is known to trigger neuroinflammation and neurodegenerative disease. However, the key components during the propagation of inflammation from the periphery to the central nervous system (CNS) remain unclear. Lipopolysaccharide (LPS) was administered to Sprague–Dawley rats to induce peripheral inflammation. An intravenous injection and an intranigral injection of clodronate liposomes were given to deplete monocytes and microglia, respectively. Recombinant CD200 fusion protein (CD200Fc) or an anti‐CD200R1 antibody was injected into the substantia nigra to manipulate the involvement of CD200 and CD200R1. Immunohistochemistry and immunofluorescence staining were used to measure microglial activation and dopaminergic neuronal loss. The expression of brain pro‐inflammatory cytokines (i.e., tumor necrosis factor alpha, IL‐1β) and CD200‐CD200R1 signaling were measured by quantitative RT‐PCR. Our data showed that the peripheral LPS injection activated the microglia and induced an increase in the levels of pro‐inflammatory cytokines (i.e., tumor necrosis factor alpha, IL‐1β). The depletion of either monocytes or microglia suppressed these inflammatory effects that were induced by peripheral LPS administration. The peripheral LPS injection increased the expression of CD200 and CD200R1 in the substantia nigra. Dopaminergic neuronal loss induced by the peripheral LPS injection was accelerated by the blockade of CD200‐CD200R1 signaling with an anti‐CD200R1 antibody and attenuated by intensifying the signaling with CD200Fc. These results highlight the importance of monocytes, microglia, and CD200‐CD200R1 signaling in the transmission of inflammation from the periphery to the CNS.