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Prepublished online as a Blood First Edition Paper on April 10, 2003; DOI 10.1182/blood-2002-09-2773. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-09-2773v1 102/3/789    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Ogilvie, P. Articles by Uguccioni, M. Search for Related Content PubMed PubMed Citation Articles by Ogilvie, P. Articles by Uguccioni, M. Related Collections Cell Adhesion and Motility Cytoskeleton Signal Transduction Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 August 2003, Vol. 102, No. 3, pp. 789-794 CHEMOKINES Eotaxin-3 is a natural antagonist for CCR2 and exerts a repulsive effect on human monocytes Patricia Ogilvie, Samantha Paoletti, Ian Clark-Lewis, and Mariagrazia Uguccioni From the Institute for Research in Biomedicine, Bellinzona, Switzerland; and Biochemical Research Center, University of British Columbia, Vancouver, Canada Eotaxin-3 (CCL26) belongs to the group of CC chemokines that attract eosinophils, basophils, and Th2 lymphocytes. Like eotaxin (CCL11) and eotaxin-2 (CCL24), eotaxin-3 mediates its activity through CCR3. Here we show that eotaxin-3 also binds to CCR2 on monocytes and CCR2-transfected cells. In contrast to monocyte chemotactic protein 1 (MCP-1; CCL2), eotaxin-3 does not trigger intracellular calcium mobilization, enzyme release, or phosphorylation of the mitogen-activated protein (MAP) kinase ERK and induces a weak chemotaxis in monocytes. Instead, eotaxin-3 inhibits MCP-1–mediated responses, thus acting as a natural antagonist for CCR2. This study also demonstrates that eotaxin-3 promotes active movement of monocytes away from a gradient of eotaxin-3 in vitro. This repellent effect is amplified when an additional gradient of MCP-1 is applied, demonstrating that the 2 mechanisms are synergistic. Eotaxin-3 effects on monocytes are largely abolished when cells are pretreated with MCP-1 or CCR2 antagonists. Like MCP-1–mediated migration, repulsion is sensitive to Bordetella pertussis toxin, indicating the involvement of Gi protein–coupled receptors. However, using transfected cells expressing CCR2 we could not detect F-actin formation or an active movement away induced by eotaxin-3, suggesting that either expression of a single receptor type is not sufficient to mediate cell repulsion or that the used transfected cell lines lack additional interaction molecules that are required for reverse migration. Eotaxin-3 was expressed by vascular endothelial cells and was essential for endothelial transmigration of eosinophils. Our data provide a mechanism by which 2 chemokine gradients that are oriented in opposite directions could cooperate in efficiently driving out monocytes from blood vessels into tissue. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Lange, D. J. Starrett, J. Goetsch, V. Gerke, and U. 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