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

• Published in: Circulation research 2001-09, Vol.89 (6), p.509-516
• Main Authors: Galt, Spencer W, Lindemann, Stephan, Medd, Don, Allen, Loren L, Kraiss, Larry W, Harris, Estelle S, Prescott, Stephen M, McIntyre, Thomas M, Weyrich, Andrew S, Zimmerman, Guy A
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Blood Platelets - cytology; Blood Platelets - drug effects; Blood Platelets - metabolism; Blotting, Western; Cell Adhesion - physiology; Chemokine CCL2 - genetics; Chemokine CCL2 - metabolism; Coculture Techniques; Collagen - metabolism; Collagen - pharmacology; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - drug effects; Humans; Inflammation; Laminin - metabolism; Laminin - pharmacology; Matrix Metalloproteinase 9 - drug effects; Matrix Metalloproteinase 9 - genetics; Matrix Metalloproteinase 9 - metabolism; Molecular and cellular biology; Monocytes - cytology; Monocytes - drug effects; Monocytes - metabolism; Protein Binding; RNA, Messenger - drug effects; RNA, Messenger - genetics; RNA, Messenger - metabolism
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/hh1801.096339

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.