title: Functional CXCR4 receptor development parallels sensitivity to HIV-1 gp120 in cultured rat astroglial cells but not in cultured rat cortical neurons.
abstract: The alpha chemokine receptor CXCR4 is used as the major coreceptor for the cell entry of T-cell-tropic human immunodeficiency virus-1 (HIV-1) isolates. Activation of this coreceptor by its natural ligand SDF1alpha is associated with an intracellular Ca(2+) increase. Because the HIV-1 glycoprotein 120 (gp120) is shedded from the surface of HIV-1-infected cells and is regarded as an injurious molecule in the pathogenesis of HIV-1-associated encephalopathy (HIVE), we investigated the effects of gp120 on the intracellular Ca(2+) regulation of astrocytes and neurons. After 5 days in vitro (DIV), SDF1alpha (50 nM) elicited a pertussis toxin-sensitive intracellular Ca(2+) increase due to Ca(2+) release from internal stores that was reduced by a blocking monoclonal antibody against the CXCR4 receptor in astrocytes and neurons. Parallel with the development of the SDF1alpha response, cells became sensitive to direct application of gp120 (1.25 microg/ml), which, similarly to SDF1alpha, elicited a transient intracellular Ca(2+) increase. However, short-term incubation with gp120 for 60 to 120 min induced a reduction of glutamate- or ATP-evoked intracellular Ca(2+) responses only in astrocytes and not in neurons, although functional CXCR4 receptors were expressed in both cell types. Therefore, our data strongly suggest that the CXCR4 receptor-mediated intracellular signaling pathway of gp120 differs in astrocytes and neurons.
authors.affiliation: Department of Neurology, Heinrich-Heine-University, Düsseldorf, Germany. koellerh@uni-dusseldorf.de
authors.forename: Hubertus
authors.initials: H
authors.lastname: Köller
authors.forename: Heiner
authors.initials: H
authors.lastname: Schaal
authors.forename: Claudia
authors.initials: C
authors.lastname: Rosenbaum
authors.forename: Margarete
authors.initials: M
authors.lastname: Czardybon
authors.forename: Hans Jürgen
authors.initials: HJ
authors.lastname: Von Giesen
authors.forename: Hans Werner
authors.initials: HW
authors.lastname: Müller
authors.forename: Gabriele
authors.initials: G
authors.lastname: Arendt
mesh_terms: D015526:AIDS Dementia Complex / Q000503:physiopathology; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology*; D015497:HIV-1; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019718:Receptors, CXCR4 / Q000096:biosynthesis / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D017154:Stromal Cells / Q000187:drug effects; D013997:Time Factors
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D015699:HIV Envelope Protein gp120; D019718:Receptors, CXCR4; D011994:Recombinant Proteins; D002118:Calcium