Characterization and visualization of [125I] stromal cell-derived factor-1alpha binding to CXCR4 receptors in rat brain and human neuroblastoma cells.
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.
Banisadr
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INSERM U. 339; Hôpital Saint-Antoine, 184 rue du Faubourg Saint-Antoine, 75571 Cedex 12, Paris, France. banisadr@st-antoine.inserm.fr
Dicou
E
E
Berbar
T
T
Rostène
W
W
Lombet
A
A
Haour
F
F
D000818:Animals; D001667:Binding, Competitive; D001923:Brain Chemistry / Q000276:immunology*; D002118:Calcium / Q000032:analysis; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000276:immunology / Q000378:metabolism*; D002831:Choroid Plexus / Q000737:chemistry / Q000276:immunology; D018728:Entorhinal Cortex / Q000737:chemistry / Q000276:immunology; D005456:Fluorescent Dyes; D006801:Humans; D007457:Iodine Radioisotopes; D009447:Neuroblastoma; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D019718:Receptors, CXCR4 / Q000276:immunology / Q000378:metabolism*; D013788:Thalamus / Q000737:chemistry / Q000276:immunology; D014407:Tumor Cells, Cultured
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D005456:Fluorescent Dyes; D007457:Iodine Radioisotopes; D019718:Receptors, CXCR4; D002118:Calcium