help button home button Am J Pathol Epitomics Buy 2 Antibodies Get 1 Free Special Offer
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Shapiro, S. D.
Right arrow Articles by Belaaouaj, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Shapiro, S. D.
Right arrow Articles by Belaaouaj, A.
(American Journal of Pathology. 2003;163:2329-2335.)
© 2003 American Society for Investigative Pathology

Neutrophil Elastase Contributes to Cigarette Smoke-Induced Emphysema in Mice

Steven D. Shapiro*, Nir M. Goldstein{dagger}, A. McGarry Houghton*{dagger}, Dale K. Kobayashi{ddagger}, Diane Kelley{ddagger} and Abderazzaq Belaaouaj{dagger}

From the Department of Pulmonary and Critical Care,* Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts; and the Departments of Medicine{dagger} and Pediatrics,{ddagger} Washington University School of Medicine at St. Louis Children’s Hospital, St. Louis, Missouri

To address the role of neutrophil elastase in pulmonary emphysema, neutrophil elastase-deficient mice and wild-type littermate controls were exposed to long-term cigarette smoke. Compared to wild-type littermates, mice that were deficient in neutrophil elastase were significantly protected (59%) from the development of emphysema. Previously, we demonstrated complete protection from emphysema in the absence of macrophage elastase. Further analysis revealed several interactions between these two elastases. Each elastase inactivated the endogenous inhibitor of the other, with neutrophil elastase degrading tissue inhibitor of metalloproteinase-1, and macrophage elastase degrading {alpha}-1-antitrypsin. Cigarette smoke-induced recruitment of both neutrophils and monocytes was impaired in the absence of neutrophil elastase. Moreover, there was less macrophage elastase activity secondary to decreased macrophage accumulation in neutrophil elastase-deficient mice. This study demonstrates a direct role for neutrophil elastase in emphysema and highlights the interdependence of the proteinases and inflammatory cells that mediate lung destruction in response to cigarette smoke.




This article has been cited by other articles:


Home page
 Am. J. Respir. Cell Mol. Bio.Home page
R. M. Tuder, J. H. Yun, and B. B. Graham
Cigarette Smoke Triggers Code Red: p21CIP1/WAF1/SDI1 Switches on Danger Responses in the Lung
Am. J. Respir. Cell Mol. Biol., July 1, 2008; 39(1): 1 - 6.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
A. M. Kaynar, A. M. Houghton, E. H. Lum, B. R. Pitt, and S. D. Shapiro
Neutrophil Elastase Is Needed for Neutrophil Emigration into Lungs in Ventilator-Induced Lung Injury
Am. J. Respir. Cell Mol. Biol., July 1, 2008; 39(1): 53 - 60.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
K. F. Chung and I. M. Adcock
Multifaceted mechanisms in COPD: inflammation, immunity, and tissue repair and destruction
Eur. Respir. J., June 1, 2008; 31(6): 1334 - 1356.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
A. Sato, Y. Hoshino, T. Hara, S. Muro, H. Nakamura, M. Mishima, and J. Yodoi
Thioredoxin-1 Ameliorates Cigarette Smoke-Induced Lung Inflammation and Emphysema in Mice
J. Pharmacol. Exp. Ther., May 1, 2008; 325(2): 380 - 388.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
L. C. Jacobsen, O. E. Sorensen, J. B. Cowland, N. Borregaard, and K. Theilgaard-Monch
The secretory leukocyte protease inhibitor (SLPI) and the secondary granule protein lactoferrin are synthesized in myelocytes, colocalize in subcellular fractions of neutrophils, and are coreleased by activated neutrophils
J. Leukoc. Biol., May 1, 2008; 83(5): 1155 - 1164.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
H. Yao, I. Edirisinghe, S.-R. Yang, S. Rajendrasozhan, A. Kode, S. Caito, D. Adenuga, and I. Rahman
Genetic Ablation of NADPH Oxidase Enhances Susceptibility to Cigarette Smoke-Induced Lung Inflammation and Emphysema in Mice
Am. J. Pathol., May 1, 2008; 172(5): 1222 - 1237.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
P. Mydel, J. M. Shipley, T. L. Adair-Kirk, D. G. Kelley, T. J. Broekelmann, R. P. Mecham, and R. M. Senior
Neutrophil Elastase Cleaves Laminin-332 (Laminin-5) Generating Peptides That Are Chemotactic for Neutrophils
J. Biol. Chem., April 11, 2008; 283(15): 9513 - 9522.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
M. A. Mall, J. R. Harkema, J. B. Trojanek, D. Treis, A. Livraghi, S. Schubert, Z. Zhou, S. M. Kreda, S. L. Tilley, E. J. Hudson, et al.
Development of Chronic Bronchitis and Emphysema in {beta}-Epithelial Na+ Channel-Overexpressing Mice
Am. J. Respir. Crit. Care Med., April 1, 2008; 177(7): 730 - 742.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
A. Churg, M. Cosio, and J. L. Wright
Mechanisms of cigarette smoke-induced COPD: insights from animal models
Am J Physiol Lung Cell Mol Physiol, April 1, 2008; 294(4): L612 - L631.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
M. A. Khan, S. Kianpour, M. R. Stampfli, and L. J. Janssen
Kinetics of in vitro bronchoconstriction in an elastolytic mouse model of emphysema
Eur. Respir. J., October 1, 2007; 30(4): 691 - 700.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. Zhang, N. Liu, S.-M. Park, Y. Wang, S. Byrne, A. E. Murmann, S. Bahr, M. E. Peter, S. T. Olson, A. Belaaouaj, et al.
Serine Protease Inhibitor 6-Deficient Mice Have Increased Neutrophil Immunity to Pseudomonas aeruginosa
J. Immunol., October 1, 2007; 179(7): 4390 - 4396.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
A. Churg, X. Wang, R. D. Wang, S. C. Meixner, E. L. G. Pryzdial, and J. L. Wright
{alpha}1-Antitrypsin Suppresses TNF-{alpha} and MMP-12 Production by Cigarette Smoke-Stimulated Macrophages
Am. J. Respir. Cell Mol. Biol., August 1, 2007; 37(2): 144 - 151.
[Abstract] [Full Text] [PDF]

Home page
 ThoraxHome page
A. Churg, R. Wang, X. Wang, P.-O. Onnervik, K. Thim, and J. L Wright
Effect of an MMP-9/MMP-12 inhibitor on smoke-induced emphysema and airway remodelling in guinea pigs
Thorax, August 1, 2007; 62(8): 706 - 713.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
G. Zhu, L. Warren, J. Aponte, A. Gulsvik, P. Bakke, The International COPD Genetics Network (ICGN) Inv, W. H. Anderson, D. A. Lomas, E. K. Silverman, and S. G. Pillai
The SERPINE2 Gene Is Associated with Chronic Obstructive Pulmonary Disease in Two Large Populations
Am. J. Respir. Crit. Care Med., July 15, 2007; 176(2): 167 - 173.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
T. Yoshida and R. M. Tuder
Pathobiology of Cigarette Smoke-Induced Chronic Obstructive Pulmonary Disease
Physiol Rev, July 1, 2007; 87(3): 1047 - 1082.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
A. Gaggar, Y. Li, N. Weathington, M. Winkler, M. Kong, P. Jackson, J. E. Blalock, and J. P. Clancy
Matrix metalloprotease-9 dysregulation in lower airway secretions of cystic fibrosis patients
Am J Physiol Lung Cell Mol Physiol, July 1, 2007; 293(1): L96 - L104.
[Abstract] [Full Text] [PDF]

Home page
 ThoraxHome page
V. Pinto-Plata, J. Toso, K. Lee, D. Park, J. Bilello, H. Mullerova, M. M De Souza, R. Vessey, and B. Celli
Profiling serum biomarkers in patients with COPD: associations with clinical parameters
Thorax, July 1, 2007; 62(7): 595 - 601.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
T. Maeno, A. M. Houghton, P. A. Quintero, S. Grumelli, C. A. Owen, and S. D. Shapiro
CD8+ T Cells Are Required for Inflammation and Destruction in Cigarette Smoke-Induced Emphysema in Mice
J. Immunol., June 15, 2007; 178(12): 8090 - 8096.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. J. Campbell and C. A. Owen
The Sulfate Groups of Chondroitin Sulfate- and Heparan Sulfate-containing Proteoglycans in Neutrophil Plasma Membranes Are Novel Binding Sites for Human Leukocyte Elastase and Cathepsin G
J. Biol. Chem., May 11, 2007; 282(19): 14645 - 14654.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol PatholHome page
J. L. Wright and A. Churg
Current Concepts in Mechanisms of Emphysema
Toxicol Pathol, January 1, 2007; 35(1): 111 - 115.
[Abstract] [Full Text] [PDF]

Home page
 PhysiologyHome page
D. G. Morris and D. Sheppard
Pulmonary Emphysema: When More is Less.
Physiology, December 1, 2006; 21(6): 396 - 403.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
K. R. Bracke, A. I. D'hulst, T. Maes, K. B. Moerloose, I. K. Demedts, S. Lebecque, G. F. Joos, and G. G. Brusselle
Cigarette Smoke-Induced Pulmonary Inflammation and Emphysema Are Attenuated in CCR6-Deficient Mice
J. Immunol., October 1, 2006; 177(7): 4350 - 4359.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
S. J. DiCamillo, S. Yang, M. V. Panchenko, P. A. Toselli, E. F. Naggar, C. B. Rich, P. J. Stone, M. A. Nugent, and M. P. Panchenko
Neutrophil elastase-initiated EGFR/MEK/ERK signaling counteracts stabilizing effect of autocrine TGF-beta on tropoelastin mRNA in lung fibroblasts
Am J Physiol Lung Cell Mol Physiol, August 1, 2006; 291(2): L232 - L243.
[Abstract] [Full Text] [PDF]

Home page
 Proc Am Thorac SocHome page
A. Shifren and R. P. Mecham
The stumbling block in lung repair of emphysema: elastic fiber assembly.
Proceedings of the ATS, July 1, 2006; 3(5): 428 - 433.
[Abstract] [Full Text] [PDF]

Home page
 ThoraxHome page
R O'Donnell, D Breen, S Wilson, and R Djukanovic
Inflammatory cells in the airways in COPD
Thorax, May 1, 2006; 61(5): 448 - 454.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
R. F. Foronjy, O. Mirochnitchenko, O. Propokenko, V. Lemaitre, Y. Jia, M. Inouye, Y. Okada, and J. M. D'Armiento
Superoxide Dismutase Expression Attenuates Cigarette Smoke- or Elastase-generated Emphysema in Mice
Am. J. Respir. Crit. Care Med., March 15, 2006; 173(6): 623 - 631.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
S. Kasagi, K. Seyama, H. Mori, S. Souma, T. Sato, T. Akiyoshi, H. Suganuma, and Y. Fukuchi
Tomato juice prevents senescence-accelerated mouse P1 strain from developing emphysema induced by chronic exposure to tobacco smoke
Am J Physiol Lung Cell Mol Physiol, February 1, 2006; 290(2): L396 - L404.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
Y. Wang, R. M. Baron, G. Zhu, M. Joo, J. W. Christman, E. S. Silverman, M. A. Perrella, R. J. Riese, and M. Cernadas
PU.1 Regulates Cathepsin S Expression in Professional APCs
J. Immunol., January 1, 2006; 176(1): 275 - 283.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
S. Takai, K. Kimura, M. Nagaki, S. Satake, K. Kakimi, and H. Moriwaki
Blockade of Neutrophil Elastase Attenuates Severe Liver Injury in Hepatitis B Transgenic Mice
J. Virol., December 15, 2005; 79(24): 15142 - 15150.
[Abstract] [Full Text] [PDF]

Home page
 GENES CELLSHome page
T. Iizuka, Y. Ishii, K. Itoh, T. Kiwamoto, T. Kimura, Y. Matsuno, Y. Morishima, A. E. Hegab, S. Homma, A. Nomura, et al.
Nrf2-deficient mice are highly susceptible to cigarette smoke-induced emphysema
Genes Cells, December 1, 2005; 10(12): 1113 - 1125.
[Abstract] [Full Text] [PDF]

Home page
 Proc Am Thorac SocHome page
C. A. Owen
Proteinases and Oxidants as Targets in the Treatment of Chronic Obstructive Pulmonary Disease
Proceedings of the ATS, November 1, 2005; 2(4): 373 - 385.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
J.-H. Lee, D.-S. Lee, E.-K. Kim, K.-H. Choe, Y.-M. Oh, T.-S. Shim, S.-E. Kim, Y.-S. Lee, and S.-D. Lee
Simvastatin Inhibits Cigarette Smoking-induced Emphysema and Pulmonary Hypertension in Rat Lungs
Am. J. Respir. Crit. Care Med., October 15, 2005; 172(8): 987 - 993.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
P. A. Martorana, R. Beume, M. Lucattelli, L. Wollin, and G. Lungarella
Roflumilast Fully Prevents Emphysema in Mice Chronically Exposed to Cigarette Smoke
Am. J. Respir. Crit. Care Med., October 1, 2005; 172(7): 848 - 853.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
M. A. Birrell, S. Wong, D. J. Hele, K. McCluskie, E. Hardaker, and M. G. Belvisi
Steroid-resistant Inflammation in a Rat Model of Chronic Obstructive Pulmonary Disease Is Associated with a Lack of Nuclear Factor-{kappa}B Pathway Activation
Am. J. Respir. Crit. Care Med., July 1, 2005; 172(1): 74 - 84.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
C. C. Taggart, C. M. Greene, T. P. Carroll, S. J. O'Neill, and N. G. McElvaney
Elastolytic Proteases: Inflammation Resolution and Dysregulation in Chronic Infective Lung Disease
Am. J. Respir. Crit. Care Med., May 15, 2005; 171(10): 1070 - 1076.
[Full Text] [PDF]

Home page
 NEJMHome page
S. D. Shapiro
COPD Unwound
N. Engl. J. Med., May 12, 2005; 352(19): 2016 - 2019.
[Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
S. D. Shapiro and E. P. Ingenito
The Pathogenesis of Chronic Obstructive Pulmonary Disease: Advances in the Past 100 Years
Am. J. Respir. Cell Mol. Biol., May 1, 2005; 32(5): 367 - 372.
[Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
U. Lappalainen, J. A. Whitsett, S. E. Wert, J. W. Tichelaar, and K. Bry
Interleukin-1{beta} Causes Pulmonary Inflammation, Emphysema, and Airway Remodeling in the Adult Murine Lung
Am. J. Respir. Cell Mol. Biol., April 1, 2005; 32(4): 311 - 318.
[Abstract] [Full Text] [PDF]

Home page
 Pharmacol. Rev.Home page
P. J. Barnes
Mediators of Chronic Obstructive Pulmonary Disease
Pharmacol. Rev., December 1, 2004; 56(4): 515 - 548.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
A. Guerassimov, Y. Hoshino, Y. Takubo, A. Turcotte, M. Yamamoto, H. Ghezzo, A. Triantafillopoulos, K. Whittaker, J. R. Hoidal, and M. G. Cosio
The Development of Emphysema in Cigarette Smoke-exposed Mice Is Strain Dependent
Am. J. Respir. Crit. Care Med., November 1, 2004; 170(9): 974 - 980.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
S. D. Swain, T. W. Wright, P. M. Degel, F. Gigliotti, and A. G. Harmsen
Neither Neutrophils nor Reactive Oxygen Species Contribute to Tissue Damage during Pneumocystis Pneumonia in Mice
Infect. Immun., October 1, 2004; 72(10): 5722 - 5732.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
A. Churg, R. D. Wang, H. Tai, X. Wang, C. Xie, and J. L. Wright
Tumor Necrosis Factor-{alpha} Drives 70% of Cigarette Smoke-induced Emphysema in the Mouse
Am. J. Respir. Crit. Care Med., September 1, 2004; 170(5): 492 - 498.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
H.-K. Jeon, H.-S. Jin, D.-H. Lee, W.-S. Choi, C.-K. Moon, Y. J. Oh, and T. H. Lee
Proteome Analysis Associated with Cadmium Adaptation in U937 Cells: IDENTIFICATION OF CALBINDIN-D28k AS A SECONDARY CADMIUM-RESPONSIVE PROTEIN THAT CONFERS RESISTANCE TO CADMIUM-INDUCED APOPTOSIS
J. Biol. Chem., July 23, 2004; 279(30): 31575 - 31583.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2003 by the American Society for Investigative Pathology.