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Blood, 1 May 2007, Vol. 109, No. 9, pp. 3856-3864. Prepublished online as a Blood First Edition Paper on December 27, 2006; DOI 10.1182/blood-2005-06-031377. This Article Full Text Full Text (PDF) Supplemental Video All Versions of this Article: blood-2005-06-031377v1 109/9/3856    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 Pizzirani, C. Articles by Di Virgilio, F. Search for Related Content PubMed PubMed Citation Articles by Pizzirani, C. Articles by Di Virgilio, F. Related Collections Immunobiology Signal Transduction Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Stimulation of P2 receptors causes release of IL-1ß–loaded microvesicles from human dendritic cells Cinzia Pizzirani1, Davide Ferrari1, Paola Chiozzi1, Elena Adinolfi1, Dorianna Sandonà2, Erika Savaglio1, and Francesco Di Virgilio1 1 Department of Experimental and Diagnostic Medicine, Section of General Pathology, and Interdisciplinary Center for the Study of Inflammation (ICSI), University of Ferrara, Italy; 2 Department of Biomedical Sciences, University of Padova, Italy Dendritic cells (DCs) are professional antigen-presenting cells that initiate the immune response by activating T lymphocytes. DCs express plasma membrane receptors for extracellular nucleotides named P2 receptors (P2Rs). Stimulation of P2Rs in these cells is known to cause chemotaxis, cytokine release, and cell death and to modulate LPS-dependent differentiation. Here we show that stimulation of the P2X7 receptor subtype (P2X7R) causes fast microvesicle shedding from DC plasma membrane. Vesicle release occurs from both immature and mature DCs; however, only vesicles from mature DCs, due to their previous exposure to LPS, contain IL-1ß. Microvesicles, whether from immature or mature DCs, also contain caspase-1 and -3 and cathepsin D. They also express the P2X7R in addition to other P2Rs and known markers of immune cells such as major histocompatibility complex II (MHC II) and CD39. Activation of the P2X7R by extracellular ATP causes IL-1ß release from the vesicle lumen. Previous studies demonstrated that high extracellular K+ inhibits IL-1ß processing and release; here we show that high ionic strength reduces microvesicle shedding when compared with a low ionic strength medium but strongly increases microvesicle IL-1ß loading. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Obregon, B. Rothen-Rutishauser, P. Gerber, P. Gehr, and L. P. Nicod Active Uptake of Dendritic Cell-Derived Exovesicles by Epithelial Cells Induces the Release of Inflammatory Mediators through a TNF-{alpha}-Mediated Pathway Am. J. Pathol., August 1, 2009; 175(2): 696 - 705. [Abstract] [Full Text] [PDF] Y. Qu, L. Ramachandra, S. Mohr, L. Franchi, C. V. Harding, G. Nunez, and G. R. Dubyak P2X7 Receptor-Stimulated Secretion of MHC Class II-Containing Exosomes Requires the ASC/NLRP3 Inflammasome but Is Independent of Caspase-1 J. Immunol., April 15, 2009; 182(8): 5052 - 5062. [Abstract] [Full Text] [PDF] E. Adinolfi, M. G. Callegari, M. Cirillo, P. Pinton, C. Giorgi, D. Cavagna, R. Rizzuto, and F. Di Virgilio Expression of the P2X7 Receptor Increases the Ca2+ Content of the Endoplasmic Reticulum, Activates NFATc1, and Protects from Apoptosis J. Biol. Chem., April 10, 2009; 284(15): 10120 - 10128. [Abstract] [Full Text] [PDF] F. M. Sansom, S. C. Robson, and E. L. Hartland Possible Effects of Microbial Ecto-Nucleoside Triphosphate Diphosphohydrolases on Host-Pathogen Interactions Microbiol. Mol. Biol. Rev., December 1, 2008; 72(4): 765 - 781. [Abstract] [Full Text] [PDF] 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] P. Pelegrin, C. Barroso-Gutierrez, and A. Surprenant P2X7 Receptor Differentially Couples to Distinct Release Pathways for IL-1{beta} in Mouse Macrophage J. Immunol., June 1, 2008; 180(11): 7147 - 7157. [Abstract] [Full Text] [PDF] Y. Qu, L. Franchi, G. Nunez, and G. R. Dubyak Nonclassical IL-1beta Secretion Stimulated by P2X7 Receptors Is Dependent on Inflammasome Activation and Correlated with Exosome Release in Murine Macrophages J. Immunol., August 1, 2007; 179(3): 1913 - 1925. [Abstract] [Full Text] [PDF]

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