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Am. J. Respir. Crit. Care Med., Volume 156, Number 1, July 1997, 240-247

Matrix Metalloproteinase Expression and Production by Alveolar Macrophages in Emphysema

GERALDINE A. FINLAY, LORRAINE R. O'DRISCOLL, KENNETH J. RUSSELL, ELIZABETH M. D'ARCY, JAMES B. MASTERSON, MUIRIS X. FITZGERALD, and CLARE M. O'CONNOR

Department of Medicine and Therapeutics, Woodview, University College Dublin, Belfield; and Department of Radiology, St. Vincents Hospital, Elm Park, Dublin, Ireland

The aim of this study was to examine the hypothesis that alveolar macrophages represent a significant source of matrix-degrading proteinases in the emphysematous lung. Macrophages from bronchoalveolar lavage fluid of 10 patients with emphysema and 10 normal volunteers were maintained in vitro for 24 h and assessed semiquantitatively for mRNA transcript levels of the matrix metalloproteinases (MMPs) gelatinases A and B, macrophage metalloelastase (MME), and interstitial collagenase. Release of these MMPs into the culture medium and secretion of neutrophil elastaselike activity was also assessed. Elevated levels of mRNA transcripts for gelatinase B (p < 0.0005) and interstitial collagenase (p < 0.0005) were observed in macrophages from emphysematous patients. Increased collagenase (p < 0.01) and neutrophil elastaselike activities (p < 0.001) were also measured in conditioned medium from patient macrophages. With gelatinase B, complexed forms of the enzyme were secreted by patient but not by control macrophages. No difference in transcript levels of gelatinase A or MME was observed between patient and control samples, and neither enzyme was detected in macrophage-conditioned media from either group. These results directly demonstrate that alveolar macrophages from the emphysematous lung produce elevated quantities of matrix-degrading enzymes with both elastolytic and collagenolytic activities.




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Y. K. Zhu, X. D. Liu, C. M. Skold, T. Umino, H. J. Wang, J. R. Spurzem, T. Kohyama, R. F. Ertl, and S. I. Rennard
Synergistic neutrophil elastase-cytokine interaction degrades collagen in three-dimensional culture
Am J Physiol Lung Cell Mol Physiol, October 1, 2001; 281(4): L868 - L878.
[Abstract] [Full Text] [PDF]

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 Eur Respir JHome page
K.F. Chung
Cytokines in chronic obstructive pulmonary disease
Eur. Respir. J., July 2, 2001; 18(34_suppl): 50S - 59s.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Cell Mol. Bio.Home page
C. Ramos, M. Montaño, J. García-Alvarez, V. Ruiz, B. D. Uhal, M. Selman, and A. Pardo
Fibroblasts from Idiopathic Pulmonary Fibrosis and Normal Lungs Differ in Growth Rate, Apoptosis, and Tissue Inhibitor of Metalloproteinases Expression
Am. J. Respir. Cell Mol. Biol., May 1, 2001; 24(5): 591 - 598.
[Abstract] [Full Text]

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 Arch. Dis. Child. Fetal Neonatal Ed.Home page
D G Sweet, K J McMahon, A E Curley, C M O'Connor, and H L Halliday
Type I collagenases in bronchoalveolar lavage fluid from preterm babies at risk of developing chronic lung disease
Arch. Dis. Child. Fetal Neonatal Ed., May 1, 2001; 84(3): 168F - 171.
[Abstract] [Full Text]

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 PhysiologyHome page
G. Miserocchi, D. Negrini, A. Passi, and G. De Luca
Development of Lung Edema: Interstitial Fluid Dynamics and Molecular Structure
Physiology, April 1, 2001; 16(2): 66 - 71.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
K. IMAI, S. S. DALAL, E. S. CHEN, R. DOWNEY, L. L. SCHULMAN, M. GINSBURG, and J. D'ARMIENTO
Human Collagenase (Matrix Metalloproteinase-1) Expression in the Lungs of Patients with Emphysema
Am. J. Respir. Crit. Care Med., March 1, 2001; 163(3): 786 - 791.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
M. Fujita, J. M. Shannon, C. G. Irvin, K. A. Fagan, C. Cool, A. Augustin, and R. J. Mason
Overexpression of tumor necrosis factor-{alpha} produces an increase in lung volumes and pulmonary hypertension
Am J Physiol Lung Cell Mol Physiol, January 1, 2001; 280(1): L39 - L49.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
M. SUGA, K. IYONAGA, T. OKAMOTO, Y. GUSHIMA, H. MIYAKAWA, T. AKAIKE, and M. ANDO
Characteristic Elevation of Matrix Metalloproteinase Activity in Idiopathic Interstitial Pneumonias
Am. J. Respir. Crit. Care Med., November 1, 2000; 162(5): 1949 - 1956.
[Abstract] [Full Text]

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 Am. J. Respir. Crit. Care Med.Home page
S. LIM, N. ROCHE, B. G. OLIVER, W. MATTOS, P. J. BARNES, and K. FAN CHUNG
Balance of Matrix Metalloprotease-9 and Tissue Inhibitor of Metalloprotease-1 from Alveolar Macrophages in Cigarette Smokers . Regulation by Interleukin-10
Am. J. Respir. Crit. Care Med., October 1, 2000; 162(4): 1355 - 1360.
[Abstract] [Full Text] [PDF]

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 NEJMHome page
P. J. Barnes
Chronic Obstructive Pulmonary Disease
N. Engl. J. Med., July 27, 2000; 343(4): 269 - 280.
[Full Text] [PDF]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
W.-Y. Su, R. H. Jaskot, J. Richards, S. R. Abramson, J. F. Woessner Jr., W.-H. Yu, and K. L. Dreher
Induction of pulmonary matrilysin expression by combustion and ambient air particles
Am J Physiol Lung Cell Mol Physiol, July 1, 2000; 279(1): L152 - L160.
[Abstract] [Full Text] [PDF]

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 ChestHome page
L. Segura-Valdez, A. Pardo, M. Gaxiola, B. D. Uhal, C. Becerril, and M. Selman
Upregulation of Gelatinases A and B, Collagenases 1 and 2, and Increased Parenchymal Cell Death in COPD
Chest, March 1, 2000; 117(3): 684 - 694.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Cell Mol. Bio.Home page
R. Dhami, B. Gilks, C. Xie, K. Zay, J. L. Wright, and A. Churg
Acute Cigarette Smoke-Induced Connective Tissue Breakdown Is Mediated by Neutrophils and Prevented by alpha 1-Antitrypsin
Am. J. Respir. Cell Mol. Biol., February 1, 2000; 22(2): 244 - 252.
[Abstract] [Full Text]

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 ChestHome page
P. J. Barnes
Mechanisms in COPD : Differences From Asthma
Chest, February 1, 2000; 117(2_suppl): 10S - 14S.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Cell Mol. Bio.Home page
T. Suga, M. Kurabayashi, Y. Sando, Y. Ohyama, T. Maeno, Y. Maeno, H. Aizawa, Y. Matsumura, T. Kuwaki, M. Kuro-o, et al.
Disruption of the klotho Gene Causes Pulmonary Emphysema in Mice . Defect in Maintenance of Pulmonary Integrity during Postnatal Life
Am. J. Respir. Cell Mol. Biol., January 1, 2000; 22(1): 26 - 33.
[Abstract] [Full Text]

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 Br. J. Ophthalmol.Home page
A. M A. El-Asrar, K. Geboes, S. A Al-Kharashi, A. A Al-Mosallam, L. Missotten, L. Paemen, and G. Opdenakker
Expression of gelatinase B in trachomatous conjunctivitis
Br. J. Ophthalmol., January 1, 2000; 84(1): 85 - 91.
[Abstract] [Full Text]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
S. Johnson and A. Knox
Autocrine production of matrix metalloproteinase-2 is required for human airway smooth muscle proliferation
Am J Physiol Lung Cell Mol Physiol, December 1, 1999; 277(6): L1109 - L1117.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
S. V. CULPITT, W. MAZIAK, S. LOUKIDIS, J. A. NIGHTINGALE, J. L. MATTHEWS, and P. J. BARNES
Effect of High Dose Inhaled Steroid on Cells, Cytokines, and Proteases in Induced Sputum in Chronic Obstructive Pulmonary Disease
Am. J. Respir. Crit. Care Med., November 1, 1999; 160(5): 1635 - 1639.
[Abstract] [Full Text]

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 Am. J. Respir. Crit. Care Med.Home page
S. D. SHAPIRO
The Macrophage in Chronic Obstructive Pulmonary Disease
Am. J. Respir. Crit. Care Med., November 1, 1999; 160(5): S29 - 32.
[Abstract] [Full Text] [PDF]

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 Am. J. Respir. Crit. Care Med.Home page
P. J. BARNES
Novel Approaches and Targets for Treatment of Chronic Obstructive Pulmonary Disease
Am. J. Respir. Crit. Care Med., November 1, 1999; 160(5): S72 - 79.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
A. F. Ofulue and M. Ko
Effects of depletion of neutrophils or macrophages on development of cigarette smoke-induced emphysema
Am J Physiol Lung Cell Mol Physiol, July 1, 1999; 277(1): L97 - L105.
[Abstract] [Full Text] [PDF]

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 ThoraxHome page
J. BRITTON and A. J KNOX
Duplicate publication, redundant publication, and disclosure of closely related publications
Thorax, May 1, 1999; 54(5): 378 - 378.
[Full Text]

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 Am. J. Respir. Cell Mol. Bio.Home page
F. Bühling, A. Gerber, C. Häckel, S. Krüger, T. Köhnlein, D. Brömme, D. Reinhold, S. Ansorge, and T. Welte
Expression of Cathepsin K in Lung Epithelial Cells
Am. J. Respir. Cell Mol. Biol., April 1, 1999; 20(4): 612 - 619.
[Abstract] [Full Text]

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 J. Immunol.Home page
M. R. Horton, S. Shapiro, C. Bao, C. J. Lowenstein, and P. W. Noble
Induction and Regulation of Macrophage Metalloelastase by Hyaluronan Fragments in Mouse Macrophages
J. Immunol., April 1, 1999; 162(7): 4171 - 4176.
[Abstract] [Full Text] [PDF]

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 ThoraxHome page
P. J Barnes
Genetics and pulmonary medicine bullet  9: Molecular genetics of chronic obstructive pulmonary disease
Thorax, March 1, 1999; 54(3): 245 - 252.
[Full Text]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
K. Zay, S. Loo, C. Xie, D. V. Devine, J. Wright, and A. Churg
Role of neutrophils and alpha 1-antitrypsin in coal- and silica-induced connective tissue breakdown
Am J Physiol Lung Cell Mol Physiol, February 1, 1999; 276(2): L269 - L279.
[Abstract] [Full Text] [PDF]


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