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Related Collections Immunobiology Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 August 2002, Vol. 100, No. 3, pp. 925-932 IMMUNOBIOLOGY Nucleotides induce chemotaxis and actin polymerization in immature but not mature human dendritic cells via activation of pertussis toxin-sensitive P2y receptors Marco Idzko, Stefan Dichmann, Davide Ferrari, Francesco Di Virgilio, Andrea la Sala, Giampiero Girolomoni, Elisabeth Panther, and Johannes Norgauer From the Department of Experimental Dermatology, University of Freiburg, Germany; 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 Laboratory of Immunology, Istituto Dermopatico dell'Immacolata, IRCCS, Rome, Italy. Dendritic cells (DCs) are considered the principal initiators of immune response because of their ability to migrate into peripheral tissues and lymphoid organs, process antigens, and activate naive T cells. There is evidence that extracellular nucleotides regulate certain functions of DCs via G-protein-coupled P2Y receptors (P2YR) and ion-channel-gated P2X receptors (P2XR). Here we investigated the chemotactic activity and analyzed the migration-associated intracellular signaling events such as actin reorganization and Ca++ transients induced by common P2R agonists such as adenosine 5'-triphosphate (ATP) and 2-methylthioadenosine triphosphate, the P2YR agonists UTP and adenosine 5'-diphosphate (ADP), or the P2XR agonists -methylenadenosine-5'-triphosphate and 2',3'-(4-benzoyl)benzoyl-ATP. The common P2R agonists and the selective P2YR agonists turned out to be potent chemotactic stimuli for immature DCs, but not for mature DCs. In contrast, P2XR agonists had only marginal chemotactic activity in both DC types. Chemotaxis was paralleled by a rise in the intracellular Ca++ concentration and by actin polymerization. Studies with pertussis toxin implicated that intracellular signaling events such as actin polymerization, mobilization of intracellular Ca++, and migration induced by nucleotides was mediated via Gi/o protein-coupled P2YR. Moreover, functional studies revealed selective down-regulation of this Gi/o protein-coupled chemotactic P2YR responsiveness during maturation, although immature and mature DCs expressed similar amounts of mRNA for the P2R subtypes (P2Y2R, P2Y4R, P2Y5R, P2Y7R, P2Y11R and P2X1R, P2X4R, P2X7R), and no major differences in respect to the mRNA expression of these receptors could be observed by semiquantitative reverse transcription and polymerase chain reaction (RT-PCR). In summary, our data describe a differential chemotactic response of immature and mature DCs to nucleotides, and lend further support to the hypothesis that P2R are a novel class of immunomodulatory plasma membrane receptors suitable for pharmacological intervention. © 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: M. Magnone, S. Bruzzone, L. Guida, G. Damonte, E. Millo, S. Scarfi, C. Usai, L. Sturla, D. Palombo, A. De Flora, et al. Abscisic Acid Released by Human Monocytes Activates Monocytes and Vascular Smooth Muscle Cell Responses Involved in Atherogenesis J. Biol. Chem., June 26, 2009; 284(26): 17808 - 17818. [Abstract] [Full Text] [PDF] N. Bodrato, L. Franco, C. Fresia, L. Guida, C. Usai, A. Salis, I. Moreschi, C. Ferraris, C. Verderio, G. Basile, et al. 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