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Secondary lymphoid tissue chemokine (CCL21) activates CXCR3 to trigger a Cl- current and chemotaxis in murine microglia

Item Type:Article
Title:Secondary lymphoid tissue chemokine (CCL21) activates CXCR3 to trigger a Cl- current and chemotaxis in murine microglia
Creators Name:Rappert, A. and Biber, K. and Nolte, C. and Lipp, M. and Schubel, A. and Lu, B. and Gerard, N.P. and Gerard, C. and Boddeke, H.W.G.M. and Kettenmann, H.
Abstract:Microglial cells represent the major immunocompetent element of the CNS and are activated by any type of brain injury or disease. A candidate for signaling neuronal injury to microglial cells is the CC chemokine ligand CCL21, given that damaged neurons express CCL21. Investigating microglia in acute slices and in culture, we demonstrate that a local application of CCL21 for 30 s triggered a Cl(-) conductance with lasted for tens of minutes. This response was sensitive to the Cl(-) channel blockers 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid and 4-acetamide-4'-isothiocyanatostilbene, 2,2'-disulfonic acid. Moreover, CCL21 triggered a chemotaxis response, which was sensitive to Cl(-) channel blockers. In microglial cells cultured from CCR7 knockout mice, CCL21 produced the same type of Cl(-) current as well as a chemotaxis response. In contrast, in microglial cells from CXCR3 knockout mice, CCL21 triggered neither a Cl(-) conductance nor a chemotaxis response after CCL21 application. We conclude that the CCL21-induced Cl(-) current is a prerequisite for the chemotaxis response mediated by the activation of CXCR3 but not CCR7 receptors, indicating that in brain CCL21 acts via a different receptor system than in lymphoid organs.
Keywords:Brain Chemistry, Cultured Cells, Chemokine CCL21, Chemokine CXCL10, CC Chemokines, CXC Chemokines, Chemotaxis, Chloride Channels, Electric Conductivity, Interferon Type II, Ligands, Macrophage Activation, Membrane Potentials, Microglia, Patch-Clamp Techniques, CXCR3 Receptors, Chemokine Receptors, Serine, Animals, Mice
Source:Journal of Immunology
Publisher:American Association of Immunologists
Page Range:3221-3226
Date:1 April 2002
Official Publication:http://www.jimmunol.org/cgi/content/abstract/168/7/3221
PubMed:View item in PubMed

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