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CXCR4 and CXCR7 form a functional receptor unit for SDF-1/CXCL12 in primary rodent microglia

: Lipfert, Jana; Ödemis, Veysel; Wagner, Daniel-Christoph; Boltze, Johannes; Engele, Jürgen


Neuropathology and applied neurobiology 39 (2013), Nr.6, S.667-680
ISSN: 0305-1846
ISSN: 1365-2990
Fraunhofer IZI ()
chemokine; Chemotaxis; cell proliferation; cell signaling; brain injury; SDF-1/CXCL12

Microglial cells have been originally identified as a target for the CXC chemokine, SDF-1, by their expression of CXCR4. More recently, it has been recognized that SDF-1 additionally binds to CXCR7, which depending on the cell type either acts as a non-classical, a classical, or a scavenger chemokine receptor. Here, we asked whether primary microglial cells additionally express CXCR7 and if so how this chemokine receptor functions in this cell type.
CXCR4 and CXCR7 expression was analyzed in cultured rat microglia and in the brain of animals with permanent MCAO by either Western blotting, RT-PCR, flow cytometry, and/or immunocytochemistry. The function of CXCR4 and CXCR7 was assessed in the presence of selective antagonists.
Cultured primary rat microglia expressed CXCR4 and CXCR7 to similar levels. Treatment with SDF-1 resulted in the activation of Erk1/2 and Akt signalling. Erk1/2 and Akt signalling were required for subsequent SDF-1-dependent promotion of microglial proliferation. By contrast, Erk1/2 signalling was sufficient for SDF-1-induced migration of microglial cells. Both SDF-1-dependent signalling and the resulting effects on microglial proliferation and migration were abrogated following pharmacological inactivation of either CXCR4 or CXCR7. Moreover, treatment of cultured microglia with LPS resulted in the co-ordinated up-regulation of CXCR4 and CXCR7 expression. Likewise, reactive microglia accumulating in the area adjacent to the lesion core in MCAO rats expressed both CXCR4 and CXCR7.
CXCR4 and CXCR7 form a functional receptor unit in microglial cells which is up-regulated during activation of microglia both in vitro and in vivo.