Zou Y R, Kottmann A H, Kuroda M, Taniuchi I, Littman D R
Division of Molecular Pathogenesis, Skirball Institute of Biomolecular Medicine, New York University Medical Center, New York 10016, USA.
Nature. 1998 Jun 11;393(6685):595-9. doi: 10.1038/31269.
Chemokines and their receptors are important in cell migration during inflammation, in the establishment of functional lymphoid microenvironments, and in organogenesis. The chemokine receptor CXCR4 is broadly expressed in cells of both the immune and the central nervous systems and can mediate migration of resting leukocytes and haematopoietic progenitors in response to its ligand, SDF-1. CXCR4 is also a major receptor for strains of human immunodeficiency virus-1 (HIV-1) that arise during progression to immunodeficiency and AIDS dementia. Here we show that mice lacking CXCR4 exhibit haematopoietic and cardiac defects identical to those of SDF-1-deficient mice, indicating that CXCR4 may be the only receptor for SDF-1. Furthermore, fetal cerebellar development in mutant animals is markedly different from that in wild-type animals, with many proliferating granule cells invading the cerebellar anlage. This is, to our knowledge, the first demonstration of the involvement of a G-protein-coupled chemokine receptor in neuronal cell migration and patterning in the central nervous system. These results may be important for designing strategies to block HIV entry into cells and for understanding mechanisms of pathogenesis in AIDS dementia.
趋化因子及其受体在炎症过程中的细胞迁移、功能性淋巴微环境的建立以及器官发生过程中起着重要作用。趋化因子受体CXCR4在免疫系统和中枢神经系统的细胞中广泛表达，并且能够介导静息白细胞和造血祖细胞对其配体SDF-1产生反应而发生迁移。CXCR4也是人类免疫缺陷病毒1型（HIV-1）毒株在发展为免疫缺陷和艾滋病痴呆过程中所使用的主要受体。在此我们表明，缺乏CXCR4的小鼠表现出与缺乏SDF-1的小鼠相同的造血和心脏缺陷，这表明CXCR4可能是SDF-1的唯一受体。此外，突变动物的胎儿小脑发育与野生型动物明显不同，有许多增殖的颗粒细胞侵入小脑原基。据我们所知，这是首次证明G蛋白偶联趋化因子受体参与中枢神经系统中神经元细胞的迁移和模式形成。这些结果对于设计阻止HIV进入细胞的策略以及理解艾滋病痴呆的发病机制可能具有重要意义。
