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Blood, 15 June 2006, Vol. 107, No. 12, pp. 4763-4769. Prepublished online as a Blood First Edition Paper on March 9, 2006; DOI 10.1182/blood-2005-04-1501. This Article Full Text Full Text (PDF) Supplemental Figures Supplemental Figures All Versions of this Article: 2005-04-1501v1 107/12/4763    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 Luft, T. Articles by Ho, A. D. Search for Related Content PubMed PubMed Citation Articles by Luft, T. Articles by Ho, A. D. Related Collections Immunobiology Cell Adhesion and Motility Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Adaptive functional differentiation of dendritic cells: integrating the network of extra- and intracellular signals Thomas Luft, Elena Rodionova, Eugene Maraskovsky, Michael Kirsch, Michael Hess, Christian Buchholtz, Martin Goerner, Max Schnurr, Radek Skoda, and Anthony D. Ho From the German Cancer Research Center, Dept of Molecular Oncology/Hematology, Heidelberg, Germany; Medizinische Klinik und Poliklinik V, University of Heidelberg, Germany; CSL Limited, Parkville, Victoria, Australia; the Ludwig Institute for Cancer Research, Melbourne, Victoria, Australia; and the Department of Internal Medicine, Division of Gastroenterology, University of Munich, Germany. Phenotypic maturation, cytokine secretion, and migration are distinct functional characteristics of dendritic cells (DCs). These functions are independently regulated by a number of extracellular variables, such as type, strength, and persistence of an array of soluble and membrane-bound mediators. Since the exact composition of these variables in response to infection may differ between individuals, the intracellular signaling pathways activated by these extracellular networks may more closely correlate with DC function and predict the course of adaptive immunity. We found that activation of p38 kinase (p38K), extracellular signal–related kinase 1/2 (ERK1/2), and phosphatidylcholine-specific phospholipase C (PC-PLC) enhanced cytokine secretion, whereas p38K, cyclic adenosine monophosphate (cAMP), and PC-PLC enhanced migration. In contrast, phosphatidylinositol 3-kinase (PI3K)/Akt-1 and cAMP inhibited cytokine secretion while ERK1/2 inhibited migration. Migration and cytokine secretion further differed in their sensitivity to inhibition over time. However, although DCs could be manipulated to express migration, cytokine secretion, or both, the level of activation or persistence of intracellular pathway signaling was not predictive. Our results suggest a modular organization of function. We hypothesize that the expression of specific DC functions integrates a large variety of activating and inhibitory variables, and is represented by the formation of a functional unit of molecular networks—the signal response module (SRM). The combined activities of these modules define the functional outcome of DC activation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Lehner, A. Stilper, P. Morhart, and W. Holter Plasticity of dendritic cell function in response to prostaglandin E2 (PGE2) and interferon-{gamma} (IFN-{gamma}) J. Leukoc. Biol., April 1, 2008; 83(4): 883 - 893. [Abstract] [Full Text] [PDF] L. Fantuzzi, F. Spadaro, C. Purificato, S. Cecchetti, F. Podo, F. Belardelli, S. Gessani, and C. Ramoni Phosphatidylcholine-specific phospholipase C activation is required for CCR5-dependent, NF-kB-driven CCL2 secretion elicited in response to HIV-1 gp120 in human primary macrophages Blood, April 1, 2008; 111(7): 3355 - 3363. [Abstract] [Full Text] [PDF] L. Frasca, M. Nasso, F. Spensieri, G. Fedele, R. Palazzo, F. Malavasi, and C. M. Ausiello IFN-{gamma} Arms Human Dendritic Cells to Perform Multiple Effector Functions J. Immunol., February 1, 2008; 180(3): 1471 - 1481. [Abstract] [Full Text] [PDF] A. S. Lo, P. Gorak-Stolinska, V. Bachy, M. A. Ibrahim, D. M. Kemeny, and J. Maher Modulation of dendritic cell differentiation by colony-stimulating factor-1: role of phosphatidylinositol 3'-kinase and delayed caspase activation J. Leukoc. Biol., December 1, 2007; 82(6): 1446 - 1454. [Abstract] [Full Text] [PDF]

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