Ischemia-induced neuronal expression of the microglia attracting chemokine secondary lymphoid-tissue chemokine (SLC)
Ischemia-induced neuronal expression of the microglia attracting chemokine secondary lymphoid-tissue chemokine (SLC)
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DOI：
10.1002/glia.1047
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发表时间：
2001-04-15
期刊：
影响因子：
6.2
通讯作者：
Boddeke, HWGM
中科院分区：
文献类型：
--
作者：
Biber, K;Sauter, A;Boddeke, HWGM
近年来的研究表明，次级淋巴组织趋化因子(SLC)在次级淋巴器官中结构性表达，控制幼稚T细胞和成熟树突状细胞的归巢。通过对小鼠脑缺血后6h至4d脑组织中SLC基因的筛选，发现SLC基因在脑缺血后6h至4d均有表达。原位杂交结合免疫组织化学染色显示，缺血区神经元表达SLC mRNA。在已知的诱导神经元死亡的各种处理后，在培养的神经元中也发现了SLC mRNA的表达，但在培养的神经胶质细胞中没有表达。SLC刺激可诱导培养的小胶质细胞内钙瞬变和趋化。由于SLC的另一种受体CXCR3编码的mRNA在小胶质细胞中未发现CCR7的表达，因此我们认为SLC对小胶质细胞的作用是由CXCR3介导的。以IP-10作为CXCR3的配基的交叉脱敏实验证实了这一假设。SLC在作用于小胶质细胞的神经元中的可诱导表达提示了SLC在神经免疫系统中的一个新的重要作用。我们认为SLC是神经元-小胶质细胞信号系统的一部分，该信号系统与脑缺血等病理条件有关。Glia 34：121-133,2001。(C)2001年Wiley-Liss，Inc.
Recently, it has been demonstrated that secondary lymphoid-tissue chemokine (SLC) is constitutively expressed in secondary lymphoid organs and controls the homing of naive T-cells and mature dendritic cells. By screening cDNA isolated from ischemic mouse brain, we found expression of SLC mRNA 6 h up to 4 days after the onset of ischemia. In situ hybridization combined with immunohistochemistry showed neurons expressing SLC mRNA in the ischemic area of the cortex. SLC mRNA expression was also found in cultured neurones after various treatments known to induce neuronal death, but not in cultured glial cells. Stimulation with SLC induced intracellular calcium transients and chemotaxis in cultured microglia. Since mRNA encoding CXCR3, an alternative receptor for SLC, but no CCR7 mRNA was found in microglia, we suggest that the effects of SLC on microglia are mediated by CXCR3. This assumption was corroborated by cross-desensitization experiments using IP-10 as a ligand for CXCR3. The inducible expression of SLC in neurones acting on microglia suggests a new and important role of SLC in the neuroimmune system. We propose that SLC is part of a neurone-microglia signaling system which is related to pathological conditions of the brain like ischemia. GLIA 34:121-133, 2001. (C) 2001 Wiley-Liss, Inc.