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Blood, 15 June 2006, Vol. 107, No. 12, pp. 4946-4953. Prepublished online as a Blood First Edition Paper on March 2, 2006; DOI 10.1182/blood-2005-07-2994. This Article Full Text Full Text (PDF) Supplemental Table and Figures All Versions of this Article: 2005-07-2994v1 107/12/4946    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 Gu, B. J. Articles by Wiley, J. S. Search for Related Content PubMed PubMed Citation Articles by Gu, B. J. Articles by Wiley, J. S. Related Collections Phagocytes Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PHAGOCYTES Rapid ATP-induced release of matrix metalloproteinase 9 is mediated by the P2X7 receptor Ben J. Gu, and James S. Wiley From the Department of Medicine, University of Sydney at Nepean Hospital, Penrith, New South Wales, Australia. Matrix metalloproteinase-9 (MMP-9) activity is required for inflammatory response, leukocyte recruitment, and tumor invasion. There is increasing evidence suggesting that the P2X7 receptor of mononuclear cells, which is activated by extracellular adenosine triphosphate (ATP), is involved in inflammatory responses. In this study, ATP caused a rapid release of MMP-9 and a moderate decrease in tissue inhibitor of metalloproteinase 1 (TIMP-1) release from human peripheral-blood mononuclear cells (PBMCs) over a 30-minute time course. The release was time- and dose-dependent and dissociated from ATP-induced cell death. BzATP, which is the most potent agonist for the P2X7 receptor, also caused a similar effect at a lower dosage. ATP-induced MMP-9 release was inhibited by the P2X7 receptor antagonists periodate oxidized ATP and KN-62, or by calcium chelators, as well as by a loss-of-function polymorphism in the P2X7 receptor, but not by brefeldin A, monensin, or cycloheximide, or by anti–tumor necrosis factor- (TNF-) or anti–interleukin-1 (IL-1) monoclonal antibodies. Results from purified subsets of PBMCs showed monocytes were the major source for MMP-9 and TIMP-1 release, and ATP remained effective in purified monocyte and T-cell populations. These observations suggest a novel role for P2X7 as a pro-inflammatory receptor involved in rapid MMP-9 release and leukocyte recruitment. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: B. J. Gu, C. Rathsam, L. Stokes, A. B. McGeachie, and J. S. Wiley Extracellular ATP dissociates nonmuscle myosin from P2X7 complex: this dissociation regulates P2X7 pore formation Am J Physiol Cell Physiol, August 1, 2009; 297(2): C430 - C439. [Abstract] [Full Text] [PDF] S. R. J. Taylor, M. Gonzalez-Begne, D. K. Sojka, J. C. Richardson, S. A. Sheardown, S. M. Harrison, C. D. Pusey, F. W. K. Tam, and J. I. Elliott Lymphocytes from P2X7-deficient mice exhibit enhanced P2X7 responses J. Leukoc. Biol., June 1, 2009; 85(6): 978 - 986. [Abstract] [Full Text] [PDF] L. Yip, T. Woehrle, R. Corriden, M. Hirsh, Y. Chen, Y. Inoue, V. Ferrari, P. A. Insel, and W. G. Junger Autocrine regulation of T-cell activation by ATP release and P2X7 receptors FASEB J, June 1, 2009; 23(6): 1685 - 1693. [Abstract] [Full Text] [PDF] C. Guo, M. Masin, O. S. Qureshi, and R. D. Murrell-Lagnado Evidence for Functional P2X4/P2X7 Heteromeric Receptors Mol. Pharmacol., December 1, 2007; 72(6): 1447 - 1456. [Abstract] [Full Text] [PDF] S. L. Fernando, B. M. Saunders, R. Sluyter, K. K. Skarratt, H. Goldberg, G. B. Marks, J. S. Wiley, and W. J. Britton A Polymorphism in the P2X7 Gene Increases Susceptibility to Extrapulmonary Tuberculosis Am. J. Respir. Crit. Care Med., February 15, 2007; 175(4): 360 - 366. [Abstract] [Full Text] [PDF]

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