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Related Collections Immunobiology Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 March 2002, Vol. 99, No. 5, pp. 1715-1722 IMMUNOBIOLOGY Dendritic cells exposed to extracellular adenosine triphosphate acquire the migratory properties of mature cells and show a reduced capacity to attract type 1 T lymphocytes Andrea la Sala, Silvia Sebastiani, Davide Ferrari, Francesco Di Virgilio, Marco Idzko, Johannes Norgauer, and Giampiero Girolomoni From the Laboratory of Immunology, Istituto Dermopatico dell'Immacolata, IRCCS, Rome, Italy; the Department of Experimental and Diagnostic Medicine, Section of General Pathology and Center for the Study of Inflammatory Diseases, University of Ferrara, Italy; and the Department of Experimental Dermatology, University of Freiburg, Germany. We previously reported that chronic stimulation with low, noncytotoxic doses of extracellular adenosine triphosphate (ATP) induced a distorted maturation of dendritic cells (DCs) and impaired their capacity to initiate T-helper (Th) 1 responses in vitro. Here, we examined the effects of ATP on chemokine-receptor expression and chemokine production by DCs. ATP strongly induced expression of CXC chemokine receptor 4 on both immature and lipopolysaccharide (LPS)-stimulated DCs and slightly up-regulated CC chemokine receptor (CCR) 7 on both DC types. In contrast, ATP reduced CCR5 expression on immature DCs. These effects were confirmed at both the messenger RNA and protein levels and were not produced by uridine triphosphate (UTP). Consistent with the changed receptor expression, ATP increased migration and intracellular calcium of immature and mature DCs to stromal-derived factor 1 (CXC ligand [CXCL] 12) and macrophage inflammatory protein [MIP] 3 (CC ligand [CCL] 19), whereas responses to MIP-1 (CCL4) were reduced. DCs are an important source of chemokines influencing recruitment of distinct T-lymphocyte subsets. ATP, but not UTP, significantly reduced LPS-induced production of interferon-inducible protein 10 (CXCL10) and regulated upon activation, normal T-cell expressed and secreted chemokine (CCL5); increased secretion of macrophage-derived chemokine (CCL22); and did not change production of thymus and activation-regulated chemokine (CCL17). Consistent with these findings, supernatants from ATP-treated mature DCs attracted Th1 and T-cytotoxic 1 cells less efficiently, whereas migration of Th2 and T cytotoxic 2 cells was not affected. Our data suggest that ATP provides a signal for enhanced lymph node localization of DCs but that it may, at the same time, diminish the capacity of DCs to amplify type 1 immune responses. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. Myrtek, T. Muller, V. Geyer, N. Derr, D. Ferrari, G. Zissel, T. Durk, S. Sorichter, W. Luttmann, M. Kuepper, et al. Activation of Human Alveolar Macrophages via P2 Receptors: Coupling to Intracellular Ca2+ Increases and Cytokine Secretion J. Immunol., August 1, 2008; 181(3): 2181 - 2188. [Abstract] [Full Text] [PDF] A. Shin, T. Toy, S. Rothenfusser, N. Robson, J. Vorac, M. Dauer, M. Stuplich, S. Endres, J. Cebon, E. Maraskovsky, et al. P2Y receptor signaling regulates phenotype and IFN-{alpha} secretion of human plasmacytoid dendritic cells Blood, March 15, 2008; 111(6): 3062 - 3069. [Abstract] [Full Text] [PDF] S. 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