Role for neuronally derived fractalkine in mediating interactions between neurons and CX3CR1-expressing microglia
Role for neuronally derived fractalkine in mediating interactions between neurons and CX3CR1-expressing microglia
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DOI：
10.1073/pnas.95.18.10896
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发表时间：
1998-09-01
影响因子：
11.1
通讯作者：
Feng, LL
中科院分区：
文献类型：
--
作者：
Harrison, JK;Jiang, Y;Feng, LL
最近鉴定的趋化因子fractalkine是趋化因子基因家族的成员，其主要由分泌的促炎分子组成。Fractalkine在结构上的区别在于CX3C基序以及跨膜和粘蛋白样结构域的存在，并在许多非造血组织（包括脑）中显示非典型组成型表达。为了深入了解趋化因子依赖性系统在中枢神经系统中的应用，我们对这种趋化因子及其受体CX3CR1进行了广泛的表征。发现大鼠脑中fractalkine的表达广泛且主要定位于神经元。在中国仓鼠卵巢细胞中表达的重组大鼠CX 3CR 1特异性结合fractalkine，并在膜锚定或可溶性形式的fractalkine蛋白存在的情况下发出信号。Fractalkine刺激小胶质细胞的趋化性和细胞内钙水平升高，这些反应被抗CX3CR1抗体阻断。面运动神经轴突切断后，面神经核中CX3CR1和Fractalkine的水平明显变化。这些包括CX3CR1表达的小胶质细胞的数量和神经元周围位置的增加，运动神经元表达的fractalkine mRNA水平的降低，以及表达的fractalkine蛋白形式的改变。这些数据描述了神经元和小胶质细胞之间的细胞通讯机制，涉及fractalkine和CX3CR1，其发生在中枢神经系统的正常和病理状态中。
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.