MMP9 production by human monocyte-derived macrophages is decreased on polymerized type I collagen

• Published in: Journal of vascular surgery Vol. 34; no. 6; pp. 1111 - 1118
• Main Authors: Lepidi, Sandro, Kenagy, Richard D., Raines, Elaine W., Chiu, Ernest S., Chait, Alan, Ross, Russell, Clowes, Alexander W.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.12.2001; Elsevier
• Subjects: Aortic Aneurysm - enzymology; Arteriosclerosis - enzymology; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cell Culture Techniques - methods; Cell Culture Techniques - standards; Cell Differentiation - physiology; Cell Size; Collagen Type I - pharmacology; Culture Media - pharmacology; Cytokines - physiology; Extracellular Space - physiology; Growth Substances - physiology; Humans; Immunohistochemistry; Macrophages - drug effects; Macrophages - enzymology; Matrix Metalloproteinase 9 - biosynthesis; Medical sciences; Monocytes - drug effects; Monocytes - enzymology; Polymers - pharmacology; Precipitin Tests; Tumor Necrosis Factor-alpha - pharmacology; Human; Prognosis; Enzyme; Pathogenesis; Cardiovascular disease; Metalloendopeptidases; Interleukin 1β; Gelatinase B; Vascular disease; Peptidases; Atherosclerotic plaque; Collagen; Atherosclerosis; Tissue rupture; Hydrolases; Platelet derived growth factor; Tumor necrosis factor α; Macrophage
• ISSN: 0741-5214; 1097-6809
• DOI: 10.1067/mva.2001.119401

The production of matrix metalloproteinases (MMPs), such as MMP9, by macrophages may be a critical factor in the rupture of unstable atherosclerotic plaques and aortic aneurysms. Therefore, we studied the role of matrix and soluble cytokines in the regulation of monocyte/macrophage expression of MMP9. Although freshly isolated monocytes synthesize little MMP9, cells cultured on tissue-culture plastic differentiate into macrophages and synthesize maximal amounts of MMP9. Differentiated macrophages cultured on plastic are unresponsive to further stimulation by interleukin 1β, tumor necrosis factor α, or platelet-derived growth factor BB. In contrast, monocytes cultured on polymerized collagen synthesize much less MMP9 than cells cultured on plastic and demonstrate a more than three-fold increase in MMP9 synthesis in response to interleukin 1β, tumor necrosis factor α, and platelet-derived growth factor BB. To determine whether the physical state of the collagen was critical for the decrease in basal synthesis of MMP9, monocytes were cultured in suspension for 5 days to allow differentiation and then seeded onto monomer or polymerized collagen. Synthesis of MMP9 was significantly decreased in cells on polymerized collagen and modestly increased in macrophages seeded on monomer collagen. These results suggest that MMP9 synthesis by macrophages in the vessel wall may be under negative control by native, polymerized collagen and that disruption of this native conformation could increase MMP9 production. In addition, cells in contact with the collagen matrix are potentially more responsive to soluble mediators such as platelet-derived growth factor, interleukin 1β, and tumor necrosis factor α. (J Vasc Surg 2001;34:1111-8.)