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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 (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 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 Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 26, 2005 Accepted February 14, 2006 Rapid ATP-induced release of matrix metalloproteinase 9 is mediated by the P2X7 receptor Ben J Gu and James S Wiley* Department of Medicine, The University of Sydney at Nepean Hospital, Penrith, New South Wales, Australia * Corresponding author; email: wileyj{at}medicine.usyd.edu.au. Matrix metalloproteinase-9 (MMP-9) activity is required for inflammatory response, leucocyte recruitment and tumor invasion. There is increasing evidence to suggest the P2X7 receptor of mononuclear cells, which is activated by extracellular ATP, is involved in inflammatory responses. In this study, ATP caused a rapid release of MMP-9 and a moderate decrease in TIMP-1 release from human peripheral blood mononuclear cells (PBMC) over a 30 min 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-TNF- or anti-IL-1 monoclonal antibodies. Results from purified subsets of PBMC 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 leucocyte 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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