Banisadr G, Dicou E, Berbar T, Rostène W, Lombet A, Haour F
INSERM U. 339; Hôpital Saint-Antoine, 184 rue du Faubourg Saint-Antoine, 75571 Cedex 12, Paris, France.
J Neuroimmunol. 2000 Oct 2;110(1-2):151-60. doi: 10.1016/s0165-5728(00)00338-6.
Stromal cell-Derived Factor-1 (SDF-1alpha), binds to the seven-transmembrane G protein-coupled CXCR4 receptor and modulates cell migration, differentiation, and proliferation. CXCR4 has been reported to be expressed in various tissues including brain. Moreover, CXCR4 has recently been shown to be one of the coreceptors for HIV-1 infection which could be implicated in HIV encephalitis. In the present study, the binding properties and autoradiographic distribution of [125I]SDF-1alpha binding to CXCR4 were characterized in the adult rat brain. SDF-1alpha binding and CXCR4 coupling system were also studied in human neuroblastoma cell line SK-N-SH. The binding of [125I]SDF-1alpha on rat brain sections was specific, time-dependent and reversible. The highest densities of CXCR4 were detected in the choroid plexus of the lateral and the dorsal third ventricle. Lower densities of [125I]SDF-1alpha binding sites were observed in various brain regions including cerebral cortex, anterior olfactory nuclei, hippocampal formation, thalamic nuclei, blood vessels and pituitary gland. In the choroid plexus, the IC(50) and K(d) of [125I]SDF-1alpha binding were respectively 0.6 nM and 0. 36 nM. Similar IC(50) values were obtained in other brain structures. A CXCR4 antagonist, bicyclam, competed with SDF-1alpha binding (30% inhibition at 10(-6) M). In SK-N-SH cells, [125I]SDF-1alpha bound to CXCR4 with a K(d) of 5.0 nM and a maximal binding capacity of 460 fmol/mg of protein. SDF-1alpha induced a rapid and transient intracellular calcium increase in SK-N-SH cells. These findings suggest that CXCR4 is highly expressed in some brain structures and have a regulatory role in the nervous system. The significance of this expression in the brain parenchyma and more specifically in the choroid plexus remains to be clarified in the normal as well as in the infected brain.
基质细胞衍生因子-1（SDF-1α）与七跨膜G蛋白偶联的CXCR4受体结合，并调节细胞迁移、分化和增殖。据报道，CXCR4在包括脑在内的各种组织中表达。此外，最近已表明CXCR4是HIV-1感染的共受体之一，这可能与HIV脑炎有关。在本研究中，在成年大鼠脑中对[125I]SDF-1α与CXCR4结合的结合特性和放射自显影分布进行了表征。还在人神经母细胞瘤细胞系SK-N-SH中研究了SDF-1α结合和CXCR4偶联系统。[125I]SDF-1α在大鼠脑切片上的结合是特异性的、时间依赖性的和可逆的。在外侧和背侧第三脑室的脉络丛中检测到最高密度的CXCR4。在包括大脑皮层、前嗅核、海马结构、丘脑核、血管和垂体在内的各种脑区中观察到较低密度的[125I]SDF-1α结合位点。在脉络丛中，[125I]SDF-1α结合的IC（50）和K（d）分别为0.6 nM和0.36 nM。在其他脑结构中获得了相似的IC（50）值。一种CXCR4拮抗剂双环胺与SDF-1α结合竞争（在10^(-6) M时抑制30%）。在SK-N-SH细胞中，[125I]SDF-1α与CXCR4结合，K（d）为5.0 nM，最大结合容量为460 fmol/mg蛋白质。SDF-1α在SK-N-SH细胞中诱导细胞内钙快速短暂增加。这些发现表明CXCR4在某些脑结构中高度表达，并在神经系统中具有调节作用。这种在脑实质尤其是脉络丛中的表达在正常以及感染脑中的意义仍有待阐明。
