Tanabe S, Heesen M, Berman M A, Fischer M B, Yoshizawa I, Luo Y, Dorf M E
Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
J Neurosci. 1997 Sep 1;17(17):6522-8. doi: 10.1523/JNEUROSCI.17-17-06522.1997.
Elevated levels of chemokines have been observed in various diseases of the CNS. Little is known, however, about how these chemokines affect parenchymal cells of the CNS. The current studies examine astrocyte chemotaxis to the mouse chemokine macrophage inflammatory protein-1alpha (MIP-1alpha). Murine astrocytes demonstrate directed migration along a chemical gradient in response to 10(-10)-10(-8) M MIP-1alpha. Peak chemotactic responses are noted at 10(-9) M. MIP-1alpha-induced astrocyte migration is specifically inhibitable with pertussis toxin, suggesting a role for Galphai proteins in the signaling process. RT-PCR and in situ hybridization were used to identify expression of the murine CCR1 MIP-1alpha receptor on astrocytes. Astrocytes contain mRNA for CCR1, but messages for CCR4 and the orphan chemokine receptor MIP-1alphaR-like#1 were not detected. The combined results suggest that a functional chemokine receptor is expressed on resident cells of the CNS. We speculate that the interactions of chemokines with astrocytes are involved in inflammatory reactions of the CNS.
在中枢神经系统的各种疾病中均观察到趋化因子水平升高。然而,关于这些趋化因子如何影响中枢神经系统的实质细胞却知之甚少。当前的研究检测了星形胶质细胞对小鼠趋化因子巨噬细胞炎性蛋白-1α(MIP-1α)的趋化作用。小鼠星形胶质细胞在10(-10)-10(-8)M MIP-1α作用下,沿化学梯度呈定向迁移。在10(-9)M时观察到最大趋化反应。百日咳毒素可特异性抑制MIP-1α诱导的星形胶质细胞迁移,提示Gαi蛋白在信号传导过程中发挥作用。采用逆转录聚合酶链反应(RT-PCR)和原位杂交技术鉴定星形胶质细胞上小鼠CCR1 MIP-1α受体的表达。星形胶质细胞含有CCR1的信使核糖核酸(mRNA),但未检测到CCR4和孤儿趋化因子受体MIP-1αR-like#1的信使。综合结果表明,中枢神经系统的驻留细胞表达功能性趋化因子受体。我们推测趋化因子与星形胶质细胞的相互作用参与了中枢神经系统的炎症反应。