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Prepublished online as a Blood First Edition Paper on May 15, 2003; DOI 10.1182/blood-2002-12-3945. This Article Full Text (PDF) All Versions of this Article: 2002-12-3945v1 102/6/1959    most recent Alert me when this article is cited Alert me if a correction is posted 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 Smit, M. J Articles by Tensen, C. P Search for Related Content PubMed PubMed Citation Articles by Smit, M. J Articles by Tensen, C. P Social Bookmarking                   What's this? Submitted January 8, 2003 Accepted April 21, 2003 CXCR3-mediated chemotaxis of human T cells is regulated by a Gi- and phospholipase C-dependent pathway and not via activation of MEK/p44/p42 MAPK nor Akt/PI-3-kinase Martine J Smit, Pauline Verdijk, Elisabeth M H van der Raaij-Helmer, Marjon Navis, Paul J Hensbergen, Rob Leurs, and Cornelis P Tensen* Division of Medicinal Chemistry, Vrije Universiteit, Amsterdam, The Netherlands Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands * Corresponding author; email: C.P.Tensen{at}lumc.nl. The chemokines CXCL9, 10 and 11 exert their action via CXC chemokine receptor-3 (CXCR3), a receptor highly expressed on activated T-cells. These IFN- induced chemokines, are thought to be crucial in directing activated T-cells to sites of inflammation. As such, they play an important role in several chronic inflammatory diseases, including ulcerative colitis, multiple sclerosis, artherosclerosis and delayed type hypersensitivity reactions of the skin. In this study, we first demonstrate that in COS-7 cells heterologously expressing CXCR3, CXCL11 is a potent activator of the pertussis toxin sensitive (PTX) p44/p42 MAPK and Akt/PI-3 kinase pathways. Next, we show that these signal transduction pathways are also operative and PTX sensitive in primary human T-cells expressing CXCR3. Importantly, abrogation of these signaling cascades by specific inhibitors did not block the migration of T-cells towards CXCR3 ligands, suggesting that MAPK and Akt activation is not crucial for CXCR3-mediated chemotaxis of T-cells. Finally, we demonstrate that CXCR3 targeting chemokines control T-cell migration via PTX sensitive, phospholipase C pathways and phosphatidylinositol kinases other than class I PI3-K. 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