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This Article Full Text Full Text (PDF) 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 McQuibban, G. A. Articles by Overall, C. M. Search for Related Content PubMed PubMed Citation Articles by McQuibban, G. A. Articles by Overall, C. M. Related Collections Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 August 2002, Vol. 100, No. 4, pp. 1160-1167 CHEMOKINES Matrix metalloproteinase processing of monocyte chemoattractant proteins generates CC chemokine receptor antagonists with anti-inflammatory properties in vivo G. Angus McQuibban, Jiang-Hong Gong, Julie P. Wong, John L. Wallace, Ian Clark-Lewis, and Christopher M. Overall From the Department of Biochemistry and Molecular Biology, the Department of Oral Biological and Medical Sciences, and the Biomedical Research Centre, University of British Columbia, Vancouver, Canada; and the Department of Pharmacology and Therapeutics, University of Calgary, Alberta, Canada. Monocyte chemoattractant protein (MCP)-3 is inactivated upon cleavage by the matrix metalloproteinase (MMP) gelatinase A (MMP-2). We investigated the susceptibility to proteolytic processing of the 4 human MCPs by 8 recombinant MMPs to determine whether MCP-3 is an isolated example or represents a general susceptibility of chemokines to proteolytic inactivation by these important inflammatory proteases. In addition to MMP-2, MCP-3 is efficiently cleaved by membrane type 1 (MT1)-MMP, the cellular activator of MMP-2, and by collagenase-1 and collagenase-3 (MMP-1, MMP-13) and stromelysin-1 (MMP-3). Specificity was shown by absence of cleavage by matrilysin (MMP-7) and the leukocytic MMPs neutrophil collagenase (MMP-8) and gelatinase B (MMP-9). The closely related chemokines MCP-1, MCP-2, and MCP-4 were not cleaved by MMP-2 or MT1-MMP, but were cleaved by MMP-1 and MMP-3 with varying efficiency. MCPs were typically cleaved between residues 4 and 5, but MCP-4 was further processed at Val7-Pro8. Synthetic MCP analogs corresponding to the MMP-cleaved forms bound CC chemokine receptor (CCR)-2 and CCR-3, but lacked chemoattractant activity in pre-B cells transfected with CCR-2 and CCR-3 or in THP-1 monocytic cells, a transformed leukemic cell line. Moreover, the truncated products of MCP-2 and MCP-4, like MCP-3, were potent antagonists of their cognate CC chemokine receptors in transwell cell migration assays in vitro. When they were injected 24 hours after the initiation of carrageenan-induced inflammation in rat paws, their in vivo antagonist activities were revealed by a greater than 66% reduction in inflammatory edema progression after 12 hours. We propose that MMPs have an important role in modulating inflammatory and immune responses by processing chemokines in wound healing and in disease. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Tarin, M. Gomez, E. Calvo, J. A. Lopez, and C. Zaragoza Endothelial Nitric Oxide Deficiency Reduces MMP-13-Mediated Cleavage of ICAM-1 in Vascular Endothelium: A Role in Atherosclerosis Arterioscler. Thromb. Vasc. Biol., January 1, 2009; 29(1): 27 - 32. 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Res., December 1, 2006; 85(12): 1074 - 1084. [Abstract] [Full Text] [PDF] J. Verstappen and J.W. Von den Hoff Tissue Inhibitors of Metalloproteinases (TIMPs): Their Biological Functions and Involvement in Oral Disease Journal of Dental Research, December 1, 2006; 85(12): 1074 - 1084. [Abstract] [Full Text] [PDF] J. K. Lim, W. Lu, O. Hartley, and A. L. DeVico N-terminal proteolytic processing by cathepsin G converts RANTES/CCL5 and related analogs into a truncated 4-68 variant J. Leukoc. Biol., December 1, 2006; 80(6): 1395 - 1404. [Abstract] [Full Text] [PDF] K. J. Greenlee, D. B. Corry, D. A. Engler, R. K. Matsunami, P. Tessier, R. G. Cook, Z. Werb, and F. Kheradmand Proteomic Identification of In Vivo Substrates for Matrix Metalloproteinases 2 and 9 Reveals a Mechanism for Resolution of Inflammation J. Immunol., November 15, 2006; 177(10): 7312 - 7321. [Abstract] [Full Text] [PDF] J. L. Taylor, J. M. Hattle, S. A. Dreitz, J. M. Troudt, L. S. Izzo, R. J. Basaraba, I. M. Orme, L. M. 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Biessen Lesional Overexpression of Matrix Metalloproteinase-9 Promotes Intraplaque Hemorrhage in Advanced Lesions But Not at Earlier Stages of Atherogenesis Arterioscler. Thromb. Vasc. Biol., February 1, 2006; 26(2): 340 - 346. [Abstract] [Full Text] [PDF] T. L. Bonfield, C. M. Swaisgood, B. P. Barna, C. F. Farver, M. S. Kavuru, and M. J. Thomassen Elevated gelatinase activity in pulmonary alveolar proteinosis: role of macrophage-colony stimulating factor J. Leukoc. Biol., January 1, 2006; 79(1): 133 - 139. [Abstract] [Full Text] [PDF] C. A. Wyatt, J. C. Geoghegan, and C. E. Brinckerhoff Short Hairpin RNA-Mediated Inhibition of Matrix Metalloproteinase-1 in MDA-231 Cells: Effects on Matrix Destruction and Tumor Growth Cancer Res., December 1, 2005; 65(23): 11101 - 11108. [Abstract] [Full Text] [PDF] J. K. Lim, J. M. Burns, W. Lu, and A. L. DeVico Multiple pathways of amino terminal processing produce two truncated variants of RANTES/CCL5 J. Leukoc. Biol., August 1, 2005; 78(2): 442 - 452. [Abstract] [Full Text] [PDF] R. D. Berahovich, Z. Miao, Y. Wang, B. Premack, M. C. Howard, and T. J. Schall Proteolytic Activation of Alternative CCR1 Ligands in Inflammation J. Immunol., June 1, 2005; 174(11): 7341 - 7351. [Abstract] [Full Text] [PDF] S. Lee, S. M. Jilani, G. V. Nikolova, D. Carpizo, and M. L. Iruela-Arispe Processing of VEGF-A by matrix metalloproteinases regulates bioavailability and vascular patterning in tumors J. Cell Biol., May 23, 2005; 169(4): 681 - 691. [Abstract] [Full Text] [PDF] C. C. Taggart, C. M. Greene, T. P. Carroll, S. J. O'Neill, and N. G. McElvaney Elastolytic Proteases: Inflammation Resolution and Dysregulation in Chronic Infective Lung Disease Am. J. Respir. Crit. Care Med., May 15, 2005; 171(10): 1070 - 1076. [Full Text] [PDF] P.-C. Lee, I-C. Ho, and T.-C. Lee Oxidative Stress Mediates Sodium Arsenite-Induced Expression of Heme Oxygenase-1, Monocyte Chemoattractant Protein-1, and Interleukin-6 in Vascular Smooth Muscle Cells Toxicol. Sci., May 1, 2005; 85(1): 541 - 550. [Abstract] [Full Text] [PDF] C. Bellehumeur, T. Collette, R. Maheux, J. Mailloux, M. Villeneuve, and A. Akoum Increased soluble interleukin-1 receptor type II proteolysis in the endometrium of women with endometriosis Hum. Reprod., May 1, 2005; 20(5): 1177 - 1184. [Abstract] [Full Text] [PDF] E. T. Choi, E. T. Collins, L. A. Marine, M. G. Uberti, H. Uchida, J. E. Leidenfrost, M. F. Khan, K. P. Boc, D. R. Abendschein, and W. C. Parks Matrix Metalloproteinase-9 Modulation by Resident Arterial Cells Is Responsible for Injury-Induced Accelerated Atherosclerotic Plaque Development in Apolipoprotein E-Deficient Mice Arterioscler. Thromb. Vasc. Biol., May 1, 2005; 25(5): 1020 - 1025. [Abstract] [Full Text] [PDF] J. ESPARZA, M. KRUSE, J. LEE, M. MICHAUD, and J. A. MADRI MMP-2 null mice exhibit an early onset and severe experimental autoimmune encephalomyelitis due to an increase in MMP-9 expression and activity FASEB J, November 1, 2004; 18(14): 1682 - 1691. [Abstract] [Full Text] [PDF] L. J. McCawley, H. C. Crawford, L. E. King Jr., J. Mudgett, and L. M. Matrisian A Protective Role for Matrix Metalloproteinase-3 in Squamous Cell Carcinoma Cancer Res., October 1, 2004; 64(19): 6965 - 6972. [Abstract] [Full Text] [PDF] Y. Li, T. Aoki, Y. Mori, M. Ahmad, H. Miyamori, T. Takino, and H. Sato Cleavage of Lumican by Membrane-Type Matrix Metalloproteinase-1 Abrogates This Proteoglycan-Mediated Suppression of Tumor Cell Colony Formation in Soft Agar Cancer Res., October 1, 2004; 64(19): 7058 - 7064.