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

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 1beta, tumor necrosis factor alpha, 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 1beta, tumor necrosis factor alpha, 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 1beta, and tumor necrosis factor alpha.

[1]  É. Allaire,et al.  Prevention of aneurysm development and rupture by local overexpression of plasminogen activator inhibitor-1. , 1998, Circulation.

[2]  Y. Shoenfeld,et al.  Superior vena cava occlusion in a patient with antiphospholipid antibody syndrome. , 1991, The Journal of rheumatology.

[3]  V. Fuster,et al.  Human monocyte-derived macrophages induce collagen breakdown in fibrous caps of atherosclerotic plaques. Potential role of matrix-degrading metalloproteinases and implications for plaque rupture. , 1995, Circulation.

[4]  P. Libby,et al.  Cytokines Regulate Vascular Functions Related to Stability of the Atherosclerotic Plaque , 1995, Journal of cardiovascular pharmacology.

[5]  S. Shapiro,et al.  Matrilysin is expressed by lipid-laden macrophages at sites of potential rupture in atherosclerotic lesions and localizes to areas of versican deposition, a proteoglycan substrate for the enzyme. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[6]  M. Aepfelbacher,et al.  Spreading of differentiating human monocytes is associated with a major increase in membrane-bound CDC42. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[7]  A. Gown,et al.  Localization of PDGF-B protein in macrophages in all phases of atherogenesis. , 1990, Science.

[8]  M. Ferguson,et al.  Interstitial collagenase (MMP-1) expression in human carotid atherosclerosis. , 1995, Circulation.

[9]  Z. Galis,et al.  Extracellular matrix modulates macrophage functions characteristic to atheroma: collagen type I enhances acquisition of resident macrophage traits by human peripheral blood monocytes in vitro. , 1998, Arteriosclerosis, thrombosis, and vascular biology.

[10]  R. Stoney,et al.  Connective tissue proteinases and inhibitors in abdominal aortic aneurysms. Involvement of the vasa vasorum in the pathogenesis of aortic aneurysms. , 1991, Arteriosclerosis and thrombosis : a journal of vascular biology.

[11]  P. Katz,et al.  Human Blood Monocytes: Characterization of Negatively Selected Human Monocytes and Their Suspension Cell Culture Derivatives , 1981, Scandinavian journal of immunology.

[12]  M. Brown,et al.  Binding site on macrophages that mediates uptake and degradation of acetylated low density lipoprotein, producing massive cholesterol deposition. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[13]  B. Baxter,et al.  Matrix metalloproteinase-2 production and its binding to the matrix are increased in abdominal aortic aneurysms. , 1998, Arteriosclerosis, thrombosis, and vascular biology.

[14]  R. Ross,et al.  Mediation of pinocytosis in cultured arterial smooth muscle and endothelial cells by platelet-derived growth factor , 1978, The Journal of cell biology.

[15]  A. Newby,et al.  Divergent regulation by growth factors and cytokines of 95 kDa and 72 kDa gelatinases and tissue inhibitors or metalloproteinases-1, -2, and -3 in rabbit aortic smooth muscle cells. , 1996, The Biochemical journal.

[16]  V. V. van Hinsbergh,et al.  Regulation of matrix metalloproteinase expression in human vein and microvascular endothelial cells. Effects of tumour necrosis factor alpha, interleukin 1 and phorbol ester. , 1993, The Biochemical journal.

[17]  A. Krettek,et al.  Effect of phenotype on the transcription of the genes for platelet-derived growth factor (PDGF) isoforms in human smooth muscle cells, monocyte-derived macrophages, and endothelial cells in vitro. , 1997, Arteriosclerosis, thrombosis, and vascular biology.

[18]  P. Libby,et al.  Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques. , 1994, The Journal of clinical investigation.

[19]  J. Rozmus,et al.  Growth factors and cytokines upregulate gelatinase expression in bone marrow CD34(+) cells and their transmigration through reconstituted basement membrane. , 1999, Blood.

[20]  D. Falcone,et al.  Role of Laminin in Matrix Induction of Macrophage Urokinase-type Plasminogen Activator and 92-kDa Metalloproteinase Expression* , 1997, The Journal of Biological Chemistry.

[21]  S. Shapiro,et al.  Induction of macrophage metalloproteinases by extracellular matrix. Evidence for enzyme- and substrate-specific responses involving prostaglandin-dependent mechanisms. , 1993, The Journal of biological chemistry.

[22]  O. Stein,et al.  Lipoprotein Uptake and Metabolism by Rat Aortic Smooth Muscle Cells in Tissue Culture , 1974, Circulation research.

[23]  J. Isner,et al.  Identification of 92-kD gelatinase in human coronary atherosclerotic lesions. Association of active enzyme synthesis with unstable angina. , 1995, Circulation.

[24]  S. Hauser,et al.  Stimulus specificity of matrix metalloproteinase dependence of human T cell migration through a model basement membrane. , 1996, Journal of immunology.

[25]  J. Pickering,et al.  Evidence for rapid accumulation and persistently disordered architecture of fibrillar collagen in human coronary restenosis lesions. , 1996, The American journal of cardiology.

[26]  N. Iscove,et al.  Platelet-derived growth factor (PDGF) activates primitive hematopoietic precursors (pre-CFCmulti) by up-regulating IL-1 in PDGF receptor-expressing macrophages. , 1993, Journal of immunology.

[27]  E. Huberman,et al.  Autocrine Regulation of Macrophage Differentiation and 92-kDa Gelatinase Production by Tumor Necrosis Factor-α via α5β1 Integrin in HL-60 Cells* , 1998, The Journal of Biological Chemistry.

[28]  A. Eisen,et al.  SV40-transformed human lung fibroblasts secrete a 92-kDa type IV collagenase which is identical to that secreted by normal human macrophages. , 1989, The Journal of biological chemistry.

[29]  M. Davies,et al.  Risk of thrombosis in human atherosclerotic plaques: role of extracellular lipid, macrophage, and smooth muscle cell content. , 1993, British heart journal.

[30]  P. Carmeliet,et al.  Urokinase-generated plasmin activates matrix metalloproteinases during aneurysm formation , 1997, Nature Genetics.

[31]  A. Böyum,et al.  Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. , 1968, Scandinavian journal of clinical and laboratory investigation. Supplementum.

[32]  P. Libby,et al.  Evidence for increased collagenolysis by interstitial collagenases-1 and -3 in vulnerable human atheromatous plaques. , 1999, Circulation.

[33]  A. Henney,et al.  Localization of stromelysin gene expression in atherosclerotic plaques by in situ hybridization. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[34]  É. Allaire,et al.  Local overexpression of TIMP-1 prevents aortic aneurysm degeneration and rupture in a rat model. , 1998, The Journal of clinical investigation.

[35]  A. Clowes,et al.  Heparin inhibits the induction of three matrix metalloproteinases (stromelysin, 92-kD gelatinase, and collagenase) in primate arterial smooth muscle cells. , 1994, The Journal of clinical investigation.

[36]  M. Reidy,et al.  Kinetics of cellular proliferation after arterial injury. I. Smooth muscle growth in the absence of endothelium. , 1983, Laboratory investigation; a journal of technical methods and pathology.

[37]  S. Shapiro,et al.  Proteinases secreted by human mononuclear phagocytes. , 1991, The Journal of rheumatology. Supplement.

[38]  Thiennu H. Vu,et al.  Gelatinase B: Structure, Regulation, and Function , 1998 .

[39]  Y. Yazaki,et al.  Expression of platelet-derived growth factor beta receptor on human monocyte-derived macrophages and effects of platelet-derived growth factor BB dimer on the cellular function. , 1993, The Journal of biological chemistry.

[40]  M. Klagsbrun,et al.  Lysophosphatidylcholine upregulates the level of heparin-binding epidermal growth factor-like growth factor mRNA in human monocytes. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[41]  A. Eisen,et al.  Neutral metalloproteinases produced by human mononuclear phagocytes. Enzyme profile, regulation, and expression during cellular development. , 1990, The Journal of clinical investigation.