Diverse Roles of Macrophage Matrix Metalloproteinases in Tissue Destruction and Tumor Growth

Summary

In the mouse, macrophage elastase is critical to macrophage proteolysis. The use of gene-targeting has uncovered both pathological roles, including destructive effects in aneurysm formation and emphysema, and physiological roles, such as tumor growth inhibition and regulation of inflammation. Translation of findings from mouse to human biology depends upon how well the disease models replicate the human conditions and the similarity of enzyme profile between species. We know that human MMP-12 is associated with these diseases, but as opposed to the mouse, other MMPs may also be of importance (MMP-9, and perhaps MMP-7, in particular). Our interpretation is that findings in mice reflect the critical role of macrophage proteolysis in these disease processes.

• References

• 1 Werb Z, Gordon S. Elastase secretion by stimulated macrophages. J Exp Med 1975; 142: 361-377.
• 2 Banda MJ, Werb Z. Mouse macrophage elastase. Purification and characterization as a metalloproteinase. Biochem J 1981; 193: 589-605.
• 3 Shapiro SD, Griffin GL, Gilbert DJ, Jenkins NA, Copeland NG, Welgus HG, Senior RM, Ley TJ. Molecular cloning, chromosomal localization and bacterial expression of a novel murine machrophage metalloelastase. J Biol Chem 1992; 267: 4664-4671.
• 4 Shapiro SD, Kobayashi D, Ley T. Cloning and characterization of a unique elastolytic metalloproteinase produced by human alveolar macrophages. J Biol Chem 1993; 268: 23824-23829.
• 5 Cornelius LA, Nehring L, Klein B, Pierce R, Bolinski M, Welgus HG. et al. Generation of angiostatin by matrix metalloproteinases: effects on neovasculariation. J Immunol. In press.
• 6 Chandler S, Cossins J, Lury J, Wells G. Macrophage metalloelastase degrades matrix and myelin proteins and processes a tumor necrosis factor-alpha fusion protein. Biochem Biophys Res Commun 1996; 228: 421-429.
• 7 Shipley JM, Wellelschmidt RL, Kobayashi DK, Ley TJ, Shapiro SD. Metalloelastase is required for macrophage-mediated proteolysis and matrix invasion in mice. Proc Natl Acad Sci USA 1996; 93: 3942-3946.
• 8 Thompson RW, Holmes DR, Mertens RA, Liao S, Botney MD, Mecham RP, Welgus HG, Parks WC. Production and localization of 92-kD gelatinase in abdominal aortic aneurysms: an elastolytic metalloproteinase expressed by aneurysm-infiltrating macrophages. J Clin Invest 1995; 96: 318-326.
• 9 Curci JA, Liao S, Huffman MD, Shapiro SD, Thompson RW. Expression and localization of macrophage elastase (matrix metaloproteinase-12) in abdominal aortic aneurysms. J Clin Invest 1998; 102: 1900-1910.
• 10 Carmeliet P, Moons L, Lijnen R, Baes M, Lemaitre V, Tipping P, Drew A, Eeckhout Y, Shapiro S, Lupu F, Collen D. Urokinase-generated plasmin activates matrix metalloproteinases during aneurysm formation. Nat Genet 1997; 17: 439-444.
• 11 Senior RM, Shapiro SD. Chronic obstructive pulmonary disease: epidemiology, pathophysiology and pathogenesis. In: Fishman’s Pulmonary Diseases and Disorders. 3rd ed. McGraw-Hill; New York: 1997
• 12 Chapman HAJ, Stone OL. 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 1984; 74: 1693-1700.
• 13 Senior RM, Griffin GL, Flisar CJ, Shapiro SD, Goldberg GI, Welgus HG. Human 92-kilodalton and 72-kilodalton type IV collagenases are elastases. J Biol Chem 1991; 266: 7870-7875.
• 14 Hautamaki RD, Kobayashi DK, Senior RM, Shapiro SD. Macrophage elastase is required for cigarette smoke-induced emphysema in mice. Science 1997; 277: 2002-2004.
• 15 Guo H, Zucker S, Gordon MK, Toole BP, Biswas C. Stimulation of matrix metalloproteinase production by recombinant extracellular matrix metalloproteinase inducer from transfected Chinese hamster ovary cells. J Biol Chem 1997; 272: 24-27.
• 16 Brooks PC, Stromblad S, Sanders LC, von Schalscha TL, Aimes RT, Stetler-Stevenson WB, Quigley JP, Cheresh DA. Localization of matrix metalloproteinase MMP-2 to the surface of invasive cells by interaction with integrin alpha V beta 3. Cell 1996; 85: 683-693.
• 17 Brooks PC, Silletti S, von Schaischa TL, Friedlander M, Cheresh DA. Disruption of angiogenesis by PEX, a noncatalytic metalloproteinase fragment with integrin binding activity. Cell 1998; 92: 391-400.
• 18 Itoh T, Tanioka M, Yoshida H, Yoshioka T, Nishimoto H, Itohara S. Reduced angiogenesis and tumor progression in gelatinase A-deficient mice. Cancer Res 1998; 58: 1048-1051.
• 19 O’Reilly M, Boehm T, Shing Y, Fukai N, Vasios G, Lane WS, Flynn E, Birkhead JR, Olsen BR, Folkman J. Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell 1997; 88: 277-285.
• 20 Gately S, Twardowski SP, Stack MS, Patrick M, Boggio L, Cundiff DL, Schnaper HW, Madison L, Volpert O, Bouck N, Enghild J, Kwaan HC, Soff GA. Human prostate carcinoma cells express enzymatic activity that converts human plasminogen to the angiogenesisis inhibitor, angiostatin. Cancer Res 1996; 56: 4887-4890.
• 21 Stathakis P, Fitzgerald M, Mathias LJ, Chesterman CN, Hogg PJ. Generation of angiostatin by reduction and proteolysis of plasmin: catalysis by a plasmin reductase secreted by cultured cells. J Biol Chem 1997; 272: 20641-20645.
• 22 Patterson BC, Sang QA. Angiostatin-converting enzyme activities of human matrilyisin (MMP-7) and gelatinase B/type IV collagenase (MMP-9). J Biol Chem 1997; 272: 28823-28825.
• 23 Cao Y, Chen A, An SSA, Ji RW, Davidson D, Llinas M. Kringle 5 of plasminogen is a novel inhibitor of endothelial cell growth. J Biol Chem 1997; 272: 22924-22928.
• 24 Dong Z, Kumar R, Yang X, Fidler IJ. Macrophage-derived metalloelastase is responsible for the generation of angiostatin in Lewis lung carcinoma. Cell 1997; 88: 801-810.
• 25 Anderson IC, Shipp MA, Docherty AJP, Teicher BA. Combination therapy including a gelatinase inhibitor and cytotoxic agent reduces local invasion and metastasis of murine Lewis lung carcinoma. Cancer Res 1996; 56: 710-715.