This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 89/6/509    most recent hh1801.096339v1 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 Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Galt, S. W. Articles by Zimmerman, G. A. Search for Related Content PubMed PubMed Citation Articles by Galt, S. W. Articles by Zimmerman, G. A. Pubmed/NCBI databases Substance via MeSH Related Collections Pathophysiology Cell biology/structural biology Gene expression Gene regulation Other Vascular biology

(Circulation Research. 2001;89:509.)
© 2001 American Heart Association, Inc.

Molecular Medicine

Differential Regulation of Matrix Metalloproteinase-9 by Monocytes Adherent to Collagen and Platelets

Spencer W. Galt, Stephan Lindemann, Don Medd, Loren L. Allen, Larry W. Kraiss, Estelle S. Harris, Stephen M. Prescott, Thomas M. McIntyre, Andrew S. Weyrich, Guy A. Zimmerman

From the Division of Vascular Surgery (S.W.G., L.W.K.), Departments of Internal Medicine (E.S.H., T.M.M., A.S.W., G.A.Z.), and Pathology (T.M.M.), the Program in Human Molecular Biology and Genetics (S.L., D.M., L.L.A., L.W.K., E.S.H., T.M.M., A.S.W., G.A.Z.), and the Huntsman Cancer Institute (S.M.P.), University of Utah, Salt Lake City, Utah.

Correspondence to Spencer W. Galt or Guy A. Zimmerman, Program in Human Molecular Biology and Genetics, University of Utah, 15 North 2030 East, Bldg 533, Room 4220, Salt Lake City, UT 84112. E-mail sgalt{at}hsc.utah.edu or guy.zimmerman@hmbg.utah.edu

Abstract — Circulating monocytes adhere to platelets and matrix proteins at sites of vascular injury, where engagement of specific surface tethering molecules mediates outside-in signaling and synthesis of gene products by the leukocytes. Here we demonstrate that interaction of isolated human monocytes with collagen induces matrix metalloproteinase-9 (MMP-9; gelatinase B) synthesis by monocytes, a process that is greatly enhanced in the presence of platelets. MMP-9 is a potent matrix degrading enzyme implicated in atherosclerotic plaque rupture, aneurysm formation, and other vascular syndromes. Synthesis of MMP-9 by monocytes is tightly regulated and synergistically increased following adhesion to collagen and platelets. Adhesion to control matrix proteins alone did not result in MMP-9 protein production and, similarly, adhesion of monocytes to platelets activated with thrombin in suspension was not sufficient to induce MMP-9 synthesis in the absence of monocyte adhesion to collagen. Interruption of intercellular contact between platelets and monocytes dramatically inhibited MMP-9 synthesis. These observations demonstrate that discrete adhesion-dependent signaling pathways govern MMP-9 synthesis by monocytes. The synthesis of MMP-9 by monocytes may be critical in vascular syndromes and other pathological processes that are dependent on dysregulated cell-cell and cell-matrix interactions.

Key Words: metalloproteinases • leukocytes • platelets • matrix • inflammation

This article has been cited by other articles:

				E. Adiguzel, P. J Ahmad, C. Franco, and M. P Bendeck Collagens in the progression and complications of atherosclerosis Vascular Medicine, February 1, 2009; 14(1): 73 - 89. [Abstract] [PDF]

				A. C. Newby Metalloproteinase Expression in Monocytes and Macrophages and its Relationship to Atherosclerotic Plaque Instability Arterioscler Thromb Vasc Biol, December 1, 2008; 28(12): 2108 - 2114. [Abstract] [Full Text] [PDF]

				S. Bournazos, J. Rennie, S. P. Hart, K. A.A. Fox, and I. Dransfield Monocyte Functional Responsiveness After PSGL-1-Mediated Platelet Adhesion Is Dependent on Platelet Activation Status Arterioscler Thromb Vasc Biol, August 1, 2008; 28(8): 1491 - 1498. [Abstract] [Full Text] [PDF]

				R. Schmidt, A. Bultmann, S. Fischel, A. Gillitzer, P. Cullen, A. Walch, P. Jost, M. Ungerer, N. D. Tolley, S. Lindemann, et al. Extracellular Matrix Metalloproteinase Inducer (CD147) Is a Novel Receptor on Platelets, Activates Platelets, and Augments Nuclear Factor {kappa}B-Dependent Inflammation in Monocytes Circ. Res., February 15, 2008; 102(3): 302 - 309. [Abstract] [Full Text] [PDF]

				V. C. Ardi, T. A. Kupriyanova, E. I. Deryugina, and J. P. Quigley Human neutrophils uniquely release TIMP-free MMP-9 to provide a potent catalytic stimulator of angiogenesis PNAS, December 18, 2007; 104(51): 20262 - 20267. [Abstract] [Full Text] [PDF]

				K. Daub, H. Langer, P. Seizer, K. Stellos, A. E. May, P. Goyal, B. Bigalke, T. Schonberger, T. Geisler, D. Siegel-Axel, et al. Platelets induce differentiation of human CD34+ progenitor cells into foam cells and endothelial cells FASEB J, December 1, 2006; 20(14): 2559 - 2561. [Abstract] [Full Text] [PDF]

				D. Alonso-Escolano, C. Medina, K. Cieslik, A. Radomski, P. Jurasz, M. J. Santos-Martinez, T. Jiffar, P. Ruvolo, and M. W. Radomski Protein Kinase C{delta} Mediates Platelet-Induced Breast Cancer Cell Invasion J. Pharmacol. Exp. Ther., July 1, 2006; 318(1): 373 - 380. [Abstract] [Full Text] [PDF]

				A. S. Weyrich, M. M. Denis, J. R. Kuhlmann-Eyre, E. D. Spencer, D. A. Dixon, G. K. Marathe, T. M. McIntyre, G. A. Zimmerman, and S. M. Prescott Dipyridamole Selectively Inhibits Inflammatory Gene Expression in Platelet-Monocyte Aggregates Circulation, February 8, 2005; 111(5): 633 - 642. [Abstract] [Full Text] [PDF]

				A. C. Newby Dual Role of Matrix Metalloproteinases (Matrixins) in Intimal Thickening and Atherosclerotic Plaque Rupture Physiol Rev, January 1, 2005; 85(1): 1 - 31. [Abstract] [Full Text] [PDF]

				M. Stefanidakis, T. Ruohtula, N. Borregaard, C. G. Gahmberg, and E. Koivunen Intracellular and Cell Surface Localization of a Complex between {alpha}M{beta}2 Integrin and Promatrix Metalloproteinase-9 Progelatinase in Neutrophils J. Immunol., June 1, 2004; 172(11): 7060 - 7068. [Abstract] [Full Text] [PDF]

				S. Mitola, M. Strasly, M. Prato, P. Ghia, and F. Bussolino IL-12 Regulates an Endothelial Cell-Lymphocyte Network: Effect on Metalloproteinase-9 Production J. Immunol., October 1, 2003; 171(7): 3725 - 3733. [Abstract] [Full Text] [PDF]

				C. B Jones, D. C Sane, and D. M Herrington Matrix metalloproteinases: A review of their structure and role in acute coronary syndrome Cardiovasc Res, October 1, 2003; 59(4): 812 - 823. [Abstract] [Full Text] [PDF]

				M. Stefanidakis, M. Bjorklund, E. Ihanus, C. G. Gahmberg, and E. Koivunen Identification of a Negatively Charged Peptide Motif within the Catalytic Domain of Progelatinases That Mediates Binding to Leukocyte {beta}2 Integrins J. Biol. Chem., September 5, 2003; 278(36): 34674 - 34684. [Abstract] [Full Text] [PDF]

				A. S. Weyrich, S. M. Prescott, and G. A. Zimmerman Platelets, Endothelial Cells, Inflammatory Chemokines, and Restenosis: Complex Signaling in the Vascular Play Book Circulation, September 17, 2002; 106(12): 1433 - 1435. [Full Text] [PDF]

				P. Jurasz, A. W.Y. Chung, A. Radomski, and M. W. Radomski Nonremodeling Properties of Matrix Metalloproteinases: The Platelet Connection Circ. Res., May 31, 2002; 90(10): 1041 - 1043. [Full Text] [PDF]

				S. W. Galt, S. Lindemann, L. Allen, D. J. Medd, J. M. Falk, T. M. McIntyre, S. M. Prescott, L. W. Kraiss, G. A. Zimmerman, and A. S. Weyrich Outside-In Signals Delivered by Matrix Metalloproteinase-1 Regulate Platelet Function Circ. Res., May 31, 2002; 90(10): 1093 - 1099. [Abstract] [Full Text] [PDF]

				A. J. Chase, M. Bond, M. F. Crook, and A. C. Newby Role of Nuclear Factor-{kappa}B Activation in Metalloproteinase-1, -3, and -9 Secretion by Human Macrophages In Vitro and Rabbit Foam Cells Produced In Vivo Arterioscler Thromb Vasc Biol, May 1, 2002; 22(5): 765 - 771. [Abstract] [Full Text] [PDF]