Biber K, Sauter A, Brouwer N, Copray S C, Boddeke H W
Department of Medical Physiology, University of Groningen, Groningen, The Netherlands.
Glia. 2001 Apr 15;34(2):121-33. doi: 10.1002/glia.1047.
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.
最近有研究表明，二级淋巴组织趋化因子（SLC）在二级淋巴器官中持续表达，并控制幼稚T细胞和成熟树突状细胞的归巢。通过筛选从缺血小鼠脑分离的cDNA，我们发现在缺血发作后6小时至4天内SLC mRNA有表达。原位杂交结合免疫组织化学显示，在皮质缺血区域有神经元表达SLC mRNA。在已知可诱导神经元死亡的各种处理后的培养神经元中也发现了SLC mRNA表达，但在培养的胶质细胞中未发现。用SLC刺激可诱导培养的小胶质细胞内的钙瞬变和趋化性。由于在小胶质细胞中未发现编码SLC的替代受体CXCR3的mRNA，但发现了CCR7 mRNA，我们认为SLC对小胶质细胞的作用是由CXCR3介导的。使用IP-10作为CXCR3配体的交叉脱敏实验证实了这一假设。神经元中SLC的可诱导表达作用于小胶质细胞，提示SLC在神经免疫系统中具有新的重要作用。我们提出SLC是神经元-小胶质细胞信号系统的一部分，该系统与脑的病理状况如缺血有关。
