Durrant Douglas M, Williams Jessica L, Daniels Brian P, Klein Robyn S
Department of Internal Medicine, Washington University School of Medicine, Campus Box 8051, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.
Department of Internal Medicine, Washington University School of Medicine, Campus Box 8051, 660 S. Euclid Avenue, St. Louis, MO 63110, USA ; Department of Anatomy and Neurobiology, Washington University School of Medicine, Campus Box 8051, 660 S. Euclid Avenue, St. Louis, MO 63110, USA ; Department of Pathology and Immunology, Washington University School of Medicine, Campus Box 8051, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.
Adv Med. 2014;2014:806741. doi: 10.1155/2014/806741. Epub 2014 Sep 30.
The discovery that chemokines and their receptors are expressed by a variety of cell types within the normal adult central nervous system (CNS) has led to an expansion of their repertoire as molecular interfaces between the immune and nervous systems. Thus, CNS chemokines are now divided into those molecules that regulate inflammatory cell migration into the CNS and those that initiate CNS repair from inflammation-mediated tissue damage. Work in our laboratory throughout the past decade has sought to elucidate how chemokines coordinate leukocyte entry and interactions at CNS endothelial barriers, under both homeostatic and inflammatory conditions, and how they promote repair within the CNS parenchyma. These studies have identified several chemokines, including CXCL12 and CXCL10, as critical regulators of leukocyte migration from perivascular locations. CXCL12 additionally plays an essential role in promoting remyelination of injured white matter. In both scenarios we have shown that chemokines serve as molecular links between inflammatory mediators and other effector molecules involved in neuroprotective processes.
趋化因子及其受体在正常成体中枢神经系统(CNS)的多种细胞类型中表达,这一发现使得它们作为免疫和神经系统之间分子界面的功能范围得到了扩展。因此,CNS趋化因子现在被分为调节炎症细胞向CNS迁移的分子和启动炎症介导的组织损伤后CNS修复的分子。在过去十年中,我们实验室的工作一直致力于阐明趋化因子如何在稳态和炎症条件下协调白细胞在CNS内皮屏障处的进入和相互作用,以及它们如何促进CNS实质内的修复。这些研究已经确定了几种趋化因子,包括CXCL12和CXCL10,是白细胞从血管周围位置迁移的关键调节因子。此外,CXCL12在促进受损白质的髓鞘再生中起着至关重要的作用。在这两种情况下,我们都表明趋化因子作为炎症介质和参与神经保护过程的其他效应分子之间的分子联系。