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Prepublished online as a Blood First Edition Paper on March 20, 2003; DOI 10.1182/blood-2002-12-3745. This Article Full Text (PDF) All Versions of this Article: 2002-12-3745v1 102/2/613    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 Schnurr, M. Articles by Maraskovsky, E. Search for Related Content PubMed PubMed Citation Articles by Schnurr, M. Articles by Maraskovsky, E. Social Bookmarking                   What's this? Submitted December 13, 2002 Accepted March 9, 2003 ATP gradients inhibit the migratory capacity of specific human dendritic cell types: implications for P2Y11 receptor signaling Max Schnurr*, Tracey Toy, Patrizia Stoitzner, Paul Cameron, Amanda Shin, Tina Beecroft, Ian D Davis, Jonathan Cebon, and Eugene Maraskovsky Tumour Biology Branch, Ludwig Institute for Cancer Research, Heidelberg, VIC, Australia Department of Microbiology, University of Melbourne, Parkville, VIC, Australia Department of Dermatology, University of Innsbruck, Innsbruck, Austria * Corresponding author; email: max.schnurr{at}ludwig.edu.au. Dendritic cells (DC) are specialized antigen-presenting cells residing in tissues where they take up antigen. Activated DC migrate via chemokine gradients from sites of inflammation to lymph nodes to stimulate T cells. At sites of inflammation, nucleotides, such as ATP, are released by activated or dying cells and can function as signaling molecules through P2 receptors (P2R). We investigated P2R expression in different DC populations and the effect of nucleotides on chemokine-directed migration. Exposure of MoDC and CD1a+ dermal DC to gradients of ATP inhibited their migratory capacity in a dose-dependent manner. Studies using P2R agonists and antagonists implicated signaling through the P2Y11R. Upon maturation, MoDC downregulated P2Y11R expression and were less sensitive to ATP-mediated inhibition of migration. In contrast, ATP did not inhibit migration of CD1c+ peripheral blood (PB) DC or IL-3R+ plasmacytoid DC. Although all four DC populations expressed mRNA for P2Y11R, calcium-flux studies showed that blood DC types were unresponsive to P2Y11R agonists. In conclusion, DC types utilize distinct P2R. The formation of ATP gradients at sites of inflammation may transiently inhibit the migration of local DC thus prolonging time of antigen encounter. 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