Abstract
Expression of matrix metalloproteinases (MMPs) is associated with a variety of destructive diseases including atherosclerotic plaque rupture, abdominal aortic aneurysms, tumor invasion, arthritis, and emphysema. This has led to the hypothesis that aberrant expression of MMPs causes tissue destruction. The macrophage, intimately associated with these inflammatory diseases is a rich source of MMPs. Interestingly, both emphysema and aortic aneurysms are associated with macrophage infiltration and elastic fiber destruction. This paper will review the potential roles of macrophage MMPs in general, and macrophage elastase (MMP12) in particular, in the development of aneurysm formation and emphysema. The role of gene targeting will be discussed as a method to perform controlled experiments in mammals to determine the effects of macrophage MMPs in these disease processes.
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References
Werb Z, Gordon S (1975) Elastase secretion by stimulated macrophages. J Exp Med 142: 361–377
Banda MJ, Werb Z (1981) Mouse macrophage elastase. Purification and characteriza-tion as a metalloproteinase. Biochem J 193: 589–605
Shapiro SD, Griffin G, Gilbert DJ, Jenkins NA, Copeland NG, Welgus HG, Senior RM, Ley TJ (1992) Molecular cloning, chromosomal localization and bacterial expression of a novel murine macrophage metalloelastase. J Biol Chem 267: 4664–4671
Shapiro SD, Kobayashi D, Ley T (1993) Cloning and characterization of a unique elastolytic metalloproteinase produced by human alveolar macrophages. J Biol Chem 268: 23824–23829
Gronski TJ, Martin R, Kobayashi DK, Walsh BC, Holman MC, Van Wart HE, Shapiro SD (1997) Hydrolysis of a broad spectrum of extracellular matrix proteins by human macrophage elastase. J Biol Chem 272: 12189–12194
Thompson RW, Mertens RA, Liao S, Holmes DR, Mecham RP, Welgus HG, Parks WC (1995) Production and localization of 92-kD gelatinase in abdominal aortic aneurysms: an elastolytic metalloproteinase expressed by aneurysm-infiltrating macrophages. J Clin Invest 96: 318–326
Curci JA, Liao S, Huffman MD, Shapiro SD, Thompson RW (1998) Elevated production of macrophage elastase (MMP-12) in abdominal aortic aneurysms and its specific localization to elastic fiber fragments within the degenerating aortic media. J Clin Invest; in press
Carmeleit P, Moons L, Lijnen R, Crawley J, Tipping P, Drew A, Eeckhout Y, Shapiro SD, Lupu F, Collen D (1997) Plasmin predisposes to atherosclerotic aneurysm formation by activation of matrix metalloproteinases. Nature Genetics 17: 439–444
Shipley JM, Wesselschmidt RL, Kobayashi DK, Ley TJ, Shapiro SD (1996) Metalloelas-tase is required for macrophage-mediated proteolysis and matrix invasion in mice. Proc Natl Acad Sci 93: 3942–3946
Bartecchi C, MacKenzie T, Schrier R (1994) The human costs of tobacco use. N Engl J Med 330: 907–912 and 975–980
Chapman HAJ, Stone OL (1984) Comparison of live human neutrophil and alveolar macrophage elastolytic activity in vitro. Relative resistance of macrophage elastolytic activity to serum and alveolar proteinase inhibitors. J Clin Invest 74: 1693–1700
Senior RM, Griffin GL, Fliszar CJ, Shapiro SD, Goldberg GI, Welgus HG (1991) Human 92-kilodalton and 72-kilodalton type IV collagenases are elastases. J Biol Chem 266: 7870–7875
Hautamaki RD, Kobayashi DK, Senior RM, Shapiro SD (1997) Macrophage elastase is required for cigarette smoke-induced emphysema in mice. Science 277: 2002–2004
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© 2000 Springer Basel AG
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Shapiro, S.D. (2000). Macrophage metalloproteinases in destructive inflammatory diseases. In: Letts, L.G., Morgan, D.W. (eds) Inflammatory Processes:. Progress in Inflammation Research. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-8468-6_7
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DOI: https://doi.org/10.1007/978-3-0348-8468-6_7
Publisher Name: Birkhäuser, Basel
Print ISBN: 978-3-0348-9580-4
Online ISBN: 978-3-0348-8468-6
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