Harrison J K, Jiang Y, Chen S, Xia Y, Maciejewski D, McNamara R K, Streit W J, Salafranca M N, Adhikari S, Thompson D A, Botti P, Bacon K B, Feng L
Department of Pharmacology and Therapeutics, University of Florida, Gainesville, FL 32610, USA.
Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10896-901. doi: 10.1073/pnas.95.18.10896.
A recently identified chemokine, fractalkine, is a member of the chemokine gene family, which consists principally of secreted, proinflammatory molecules. Fractalkine is distinguished structurally by the presence of a CX3C motif as well as transmembrane spanning and mucin-like domains and shows atypical constitutive expression in a number of nonhematopoietic tissues, including brain. We undertook an extensive characterization of this chemokine and its receptor CX3CR1 in the brain to gain insights into use of chemokine-dependent systems in the central nervous system. Expression of fractalkine in rat brain was found to be widespread and localized principally to neurons. Recombinant rat CX3CR1, as expressed in Chinese hamster ovary cells, specifically bound fractalkine and signaled in the presence of either membrane-anchored or soluble forms of fractalkine protein. Fractalkine stimulated chemotaxis and elevated intracellular calcium levels of microglia; these responses were blocked by anti-CX3CR1 antibodies. After facial motor nerve axotomy, dramatic changes in the levels of CX3CR1 and fractalkine in the facial nucleus were evident. These included increases in the number and perineuronal location of CX3CR1-expressing microglia, decreased levels of motor neuron-expressed fractalkine mRNA, and an alteration in the forms of fractalkine protein expressed. These data describe mechanisms of cellular communication between neurons and microglia, involving fractalkine and CX3CR1, which occur in both normal and pathological states of the central nervous system.
一种最近发现的趋化因子——fractalkine，是趋化因子基因家族的成员，该家族主要由分泌型促炎分子组成。Fractalkine在结构上的特点是存在一个CX3C基序以及跨膜结构域和黏蛋白样结构域，并且在包括脑在内的许多非造血组织中呈现非典型的组成性表达。我们对这种趋化因子及其在脑中的受体CX3CR1进行了广泛的表征，以深入了解中枢神经系统中趋化因子依赖性系统的用途。发现fractalkine在大鼠脑中广泛表达，主要定位于神经元。在中国仓鼠卵巢细胞中表达的重组大鼠CX3CR1能特异性结合fractalkine，并在膜锚定形式或可溶性形式的fractalkine蛋白存在时发出信号。Fractalkine刺激小胶质细胞的趋化作用并提高其细胞内钙水平；这些反应被抗CX3CR1抗体阻断。面神经轴突切断后，面神经核中CX3CR1和fractalkine水平发生了显著变化。这些变化包括表达CX3CR1的小胶质细胞数量增加及其在神经元周围的定位、运动神经元表达的fractalkine mRNA水平降低以及所表达的fractalkine蛋白形式的改变。这些数据描述了神经元与小胶质细胞之间细胞通讯的机制，涉及fractalkine和CX3CR1，它们发生在中枢神经系统的正常和病理状态中。
