Characterization and visualization of [I-125] stromal cell-derived factor-1 alpha binding to CXCR4 receptors in rat brain and human neuroblastoma cells

Stromal cell-Derived Factor-1 (SDF-1 alpha), binds to the seven-transmembra ne G protein-coupled CXCR4 receptor and modulates cell migration, different iation, and proliferation. CXCR4 has been reported to be expressed in vario us tissues including brain. Moreover, CXCR4 has recently been shown to be o ne of the coreceptors for HIV-1 infection which could be implicated in HIV encephalitis. In the present study, the binding properties and autoradiogra phic distribution of [I-125]SDF-1 alpha: binding to CXCR4 were characterize d in the adult rat brain. SDF-1 alpha binding and CXCR4 coupling system wer e also studied in human neuroblastoma cell line SK-N-SH. The binding of [I- 125]SDF-1 alpha on rat brain sections was specific, time-dependent and reve rsible. The highest densities of CXCR4 were detected in the choroid plexus of the lateral and the dorsal third ventricle. Lower densities of [I-125]SD F-1 alpha binding sites were observed in various brain regions including ce rebral cortex, anterior olfactory nuclei, hippocampal formation, thalamic n uclei, blood vessels and pituitary gland. In the choroid plexus, the IC50 a nd K-d of [I-125]SDF-1 alpha binding were respectively 0.6 nM and 0.36 nM. Similar IC50 values were obtained in other brain structures. A CXCR4 antago nist, bicyclam, competed with SDF-1 alpha binding (30% inhibition at 10(-6) M). In SK-N-SH cells, [I-125]SDF-1 alpha bound to CXCR4 with a K-d of 5.0 nM and a maximal binding capacity of 460 fmol/mg of protein. SDF-1 alpha in duced a rapid and transient intracellular calcium increase in SK-N-SH cells . These findings suggest that CXCR4 is highly expressed in some brain struc tures and have a regulatory role in the nervous system. The significance of this expression in the brain parenchyma and more specifically in the choro id plexus remains to be clarified in the normal as well as in the infected brain. (C) 2000 Elsevier Science B.V. All rights reserved.