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Science 26 September 1997:
Vol. 277. no. 5334, pp. 2002 - 2004
DOI: 10.1126/science.277.5334.2002
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Reports

Requirement for Macrophage Elastase for Cigarette Smoke-Induced Emphysema in Mice

R. Dean Hautamaki, Dale K. Kobayashi, Robert M. Senior, Steven D. Shapiro *

To determine which proteinases are responsible for the lung destruction characteristic of pulmonary emphysema, macrophage elastase-deficient (MME-/-) mice were subjected to cigarette smoke. In contrast to wild-type mice, MME-/- mice did not have increased numbers of macrophages in their lungs and did not develop emphysema in response to long-term exposure to cigarette smoke. Smoke-exposed MME-/- mice that received monthly intratracheal instillations of monocyte chemoattractant protein-1 showed accumulation of alveolar macrophages but did not develop air space enlargement. Thus, macrophage elastase is probably sufficient for the development of emphysema that results from chronic inhalation of cigarette smoke.

Departments of Internal Medicine, and Cell Biology and Physiology, Washington University School of Medicine at Barnes-Jewish Hospital, St. Louis, MO 63110, USA.
*   To whom correspondence should be addressed. E-mail: sshapiro{at}imgate.wustl.edu

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Role of Matrix Metalloproteinases in the Inflammatory Response in Human Airway Cell-Based Assays and in Rodent Models of Airway Disease.
M. A. Birrell, S. Wong, A. Dekkak, J. De Alba, S. Haj-Yahia, and M. G. Belvisi (2006)
J. Pharmacol. Exp. Ther. 318, 741-750
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Interaction of HIV Tat and matrix metalloproteinase in HIV neuropathogenesis: a new host defense mechanism.
J. Rumbaugh, J. Turchan-Cholewo, D. Galey, C. St. Hillaire, C. Anderson, K. Conant, and A. Nath (2006)
FASEB J 20, 1736-1738
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Extracellular matrix in lung disease. Proceedings of the Twenty-First Transatlantic Airway Conference..
S. D. Shapiro (2006)
Proceedings of the ATS 3, 397-455
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Progress in chronic obstructive pulmonary disease genetics..
E. K. Silverman (2006)
Proceedings of the ATS 3, 405-408
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Role of tumour necrosis factor-{alpha} receptor p75 in cigarette smoke-induced pulmonary inflammation and emphysema.
A. I. D'hulst, K. R. Bracke, T. Maes, J. L. De Bleecker, R. A. Pauwels, G. F. Joos, and G. G. Brusselle (2006)
Eur. Respir. J. 28, 102-112
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Macrophage elastase (matrix metalloproteinase-12) suppresses growth of lung metastases..
A. M. Houghton, J. L. Grisolano, M. L. Baumann, D. K. Kobayashi, R. D. Hautamaki, L. C. Nehring, L. A. Cornelius, and S. D. Shapiro (2006)
Cancer Res. 66, 6149-6155
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Involvement of MMP-12 and phosphodiesterase type 4 in cigarette smoke-induced inflammation in mice.
O. Leclerc, V. Lagente, J-M. Planquois, C. Berthelier, M. Artola, T. Eichholtz, C. P. Bertrand, and F. Schmidlin (2006)
Eur. Respir. J. 27, 1102-1109
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Oxidants and Signaling by Mitogen-Activated Protein Kinases in Lung Epithelium.
B. T. Mossman, K. M. Lounsbury, and S. P. Reddy (2006)
Am. J. Respir. Cell Mol. Biol. 34, 666-669
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Expression of the Reverse Tetracycline-Transactivator Gene Causes Emphysema-Like Changes in Mice.
T. H. Sisson, J. M. Hansen, M. Shah, K. E. Hanson, M. Du, T. Ling, R. H. Simon, and P. J. Christensen (2006)
Am. J. Respir. Cell Mol. Biol. 34, 552-560
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Differential protease, innate immunity, and NF-{kappa}B induction profiles during lung inflammation induced by subchronic cigarette smoke exposure in mice.
R. Vlahos, S. Bozinovski, J. E. Jones, J. Powell, J. Gras, A. Lilja, M. J. Hansen, R. C. Gualano, L. Irving, and G. P. Anderson (2006)
Am J Physiol Lung Cell Mol Physiol 290, L931-L945
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Novel Transgenic Rabbit Model Sheds Light on the Puzzling Role of Matrix Metalloproteinase-12 in Atherosclerosis.
M. Tjwa, P. Carmeliet, and L. Moons (2006)
Circulation 113, 1929-1932
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Macrophage Metalloelastase Accelerates the Progression of Atherosclerosis in Transgenic Rabbits.
J. Liang, E. Liu, Y. Yu, S. Kitajima, T. Koike, Y. Jin, M. Morimoto, K. Hatakeyama, Y. Asada, T. Watanabe, et al. (2006)
Circulation 113, 1993-2001
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Development of Selective Inhibitors and Substrate of Matrix Metalloproteinase-12.
L. Devel, V. Rogakos, A. David, A. Makaritis, F. Beau, P. Cuniasse, A. Yiotakis, and V. Dive (2006)
J. Biol. Chem. 281, 11152-11160
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Cigarette Smoke-induced Emphysema: A Role for the B Cell?.
B. W. A. van der Strate, D. S. Postma, C.-A. Brandsma, B. N. Melgert, M. A. Luinge, M. Geerlings, M. N. Hylkema, A. van den Berg, W. Timens, and H. A. M. Kerstjens (2006)
Am. J. Respir. Crit. Care Med. 173, 751-758
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Superoxide Dismutase Expression Attenuates Cigarette Smoke- or Elastase-generated Emphysema in Mice.
R. F. Foronjy, O. Mirochnitchenko, O. Propokenko, V. Lemaitre, Y. Jia, M. Inouye, Y. Okada, and J. M. D'Armiento (2006)
Am. J. Respir. Crit. Care Med. 173, 623-631
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Matrix metalloproteinases in destructive pulmonary pathology.
P T G Elkington and J S Friedland (2006)
Thorax 61, 259-266
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Elevated MMP-12 protein levels in induced sputum from patients with COPD.
I K Demedts, A Morel-Montero, S Lebecque, Y Pacheco, D Cataldo, G F Joos, R A Pauwels, and G G Brusselle (2006)
Thorax 61, 196-201
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Failure of Elastic Fiber Homeostasis Leads to Pelvic Floor Disorders.
X. Liu, Y. Zhao, B. Pawlyk, M. Damaser, and T. Li (2006)
Am. J. Pathol. 168, 519-528
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