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Blood, 1 September 2008, Vol. 112, No. 5, pp. 1822-1831. Prepublished online as a Blood First Edition Paper on June 17, 2008; DOI 10.1182/blood-2008-02-136325. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-02-136325v1 112/5/1822    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 Novitskiy, S. V. Articles by Dikov, M. M. Search for Related Content PubMed PubMed Citation Articles by Novitskiy, S. V. Articles by Dikov, M. M. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Adenosine receptors in regulation of dendritic cell differentiation and function Sergey V. Novitskiy1,2, Sergey Ryzhov2,3, Rinat Zaynagetdinov2,3, Anna E. Goldstein4,5, Yuhui Huang1,2, Oleg Y. Tikhomirov1,2, Michael R. Blackburn6, Italo Biaggioni2,4,5, David P. Carbone1,2, Igor Feoktistov2,3,5, and Mikhail M. Dikov1,2 1 Division of Hematology/Oncology, 2 Department of Medicine, 3 Division of Cardiology, 4 Division of Clinical Pharmacology, and 5 Department of Pharmacology, Vanderbilt University, Nashville, TN; and 6 Department of Biochemistry and Molecular Biology, University of Texas-Houston Medical School Differentiation of functional dendritic cells (DCs) critically depends on the microenvironment. DCs differentiate in hypoxic tumor sites and inflamed or damaged tissue. Because local concentrations of adenosine reach high physiologically relevant levels in these conditions, we assessed the expression of adenosine receptors and the effect of their activation on differentiation of human monocytes and mouse peritoneal macrophages and hematopoietic progenitor cells (HPCs) into myeloid DCs. Stimulation of adenosine receptors skews DC differentiation toward a distinct cell population characterized by expression of both DC and monocyte/macrophage cell surface markers. Pharmacologic analysis and experiments with cells from A2B adenosine receptor knockout mice identified A2B receptor as the mediator of adenosine effects on DCs. Unlike normal myeloid DCs, adenosine-differentiated DCs have impaired allostimulatory activity and express high levels of angiogenic, pro-inflammatory, immune suppressor, and tolerogenic factors, including VEGF, IL-8, IL-6, IL-10, COX-2, TGF-β, and IDO. They promoted tumor growth if injected into tumors implanted in mice. Using adenosine desaminase knockout animals, we showed that DCs with proangiogenic phenotype are highly abundant under conditions associated with elevated levels of extracellular adenosine in vivo. Adenosine signaling through A2B receptor is an important factor of aberrant DC differentiation and generation of tolerogenic, angiogenic, and proinflammatory cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Ohta, A. Ohta, M. Madasu, R. Kini, M. Subramanian, N. Goel, and M. Sitkovsky A2A Adenosine Receptor May Allow Expansion of T Cells Lacking Effector Functions in Extracellular Adenosine-Rich Microenvironments J. Immunol., November 1, 2009; 183(9): 5487 - 5493. [Abstract] [Full Text] [PDF] J. M. Wilson, W. G. Ross, O. N. Agbai, R. Frazier, R. A. Figler, J. Rieger, J. Linden, and P. B. Ernst The A2B Adenosine Receptor Impairs the Maturation and Immunogenicity of Dendritic Cells J. Immunol., April 15, 2009; 182(8): 4616 - 4623. [Abstract] [Full Text] [PDF] A. Curti, S. Trabanelli, V. Salvestrini, M. Baccarani, and R. M. Lemoli The role of indoleamine 2,3-dioxygenase in the induction of immune tolerance: focus on hematology Blood, March 12, 2009; 113(11): 2394 - 2401. [Abstract] [Full Text] [PDF]

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