help button home button Am J Pathol Epitomics, Inc.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Material
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 Chua, F.
Right arrow Articles by Laurent, G. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chua, F.
Right arrow Articles by Laurent, G. J.
(American Journal of Pathology. 2007;170:65-74.)
© 2007 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2007.060352

Mice Lacking Neutrophil Elastase Are Resistant to Bleomycin-Induced Pulmonary Fibrosis

Felix Chua*, Sarah E. Dunsmore*{dagger}, Peter H. Clingen{ddagger}, Steven E. Mutsaers*, Steven D. Shapiro{dagger}, Anthony W. Segal*, Jürgen Roes§ and Geoffrey J. Laurent*

From the Departments of Medicine,* Oncology,{ddagger} and Immunology and Molecular Pathology,§ Royal Free and University College Medical School, London, United Kingdom; and the Department of Medicine (Pulmonary),{dagger} Brigham and Women’s Hospital, Boston, Massachusetts

Neutrophil elastase is a serine protease stored in the azurophilic granules of leukocytes. It has been implicated in the pathology of several lung diseases and is generally presumed to contribute to the tissue destruction and extracellular matrix damage associated with these conditions. To delineate the role of neutrophil elastase in pulmonary inflammation and fibrosis, neutrophil elastase-null mice were intratracheally instilled with bleomycin. In neutrophil elastase-null mice, biochemical and morphological characteristics of pulmonary fibrosis were attenuated for at least 60 days after bleomycin administration despite a typical response to bleomycin as evidenced by assessment of indices of DNA and cell damage. Neutrophil burden of bleomycin-treated wild-type and neutrophil elastase-null mice was comparable, and marked neutrophilic alveolitis was manifest in bleomycin-treated neutrophil elastase-null mice. An absence of immunostaining for active transforming growth factor (TGF)-ß in lung tissue from bleomycin-treated neutrophil elastase-null mice suggested a defect in TGF-ß activation, which was confirmed by biochemical assessment of TGF-ß levels in bronchoalveolar lavage fluid and lung tissue. These data point to novel and unexpected fibrogenic consequences of neutrophil elastase activity in the inflamed lung.




This article has been cited by other articles:


Home page
 Am. J. Respir. Cell Mol. Bio.Home page
R. C. Russo, R. Guabiraba, C. C. Garcia, L. S. Barcelos, E. Roffe, A. L. S. Souza, F. A. Amaral, D. Cisalpino, G. D. Cassali, A. Doni, et al.
Role of the Chemokine Receptor CXCR2 in Bleomycin-Induced Pulmonary Inflammation and Fibrosis
Am. J. Respir. Cell Mol. Biol., April 1, 2009; 40(4): 410 - 421.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
E. Kolaczkowska, W. Grzybek, N. van Rooijen, H. Piccard, B. Plytycz, B. Arnold, and G. Opdenakker
Neutrophil elastase activity compensates for a genetic lack of matrix metalloproteinase-9 (MMP-9) in leukocyte infiltration in a model of experimental peritonitis
J. Leukoc. Biol., March 1, 2009; 85(3): 374 - 381.
[Abstract] [Full Text] [PDF]

Home page
 The Journal of RheumatologyHome page
T. HARA, F. OGAWA, K. YANABA, Y. IWATA, E. MUROI, K. KOMURA, M. TAKENAKA, K. SHIMIZU, M. HASEGAWA, M. FUJIMOTO, et al.
Elevated Serum Concentrations of Polymorphonuclear Neutrophilic Leukocyte Elastase in Systemic Sclerosis: Association with Pulmonary Fibrosis
J Rheumatol, January 1, 2009; 36(1): 99 - 105.
[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
 Proc Am Thorac SocHome page
G. J. Laurent, R. J. McAnulty, M. Hill, and R. Chambers
Escape from the Matrix: Multiple Mechanisms for Fibroblast Activation in Pulmonary Fibrosis
Proceedings of the ATS, April 15, 2008; 5(3): 311 - 315.
[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
 Exp Biol MedHome page
T. Kisseleva and D. A. Brenner
Mechanisms of Fibrogenesis
Exp Biol Med, February 1, 2008; 233(2): 109 - 122.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
N. Pottier, C. Chupin, V. Defamie, B. Cardinaud, R. Sutherland, G. Rios, F. Gauthier, P. J. Wolters, Y. Berthiaume, P. Barbry, et al.
Relationships between Early Inflammatory Response to Bleomycin and Sensitivity to Lung Fibrosis: A Role for Dipeptidyl-Peptidase I and Tissue Inhibitor of Metalloproteinase-3?
Am. J. Respir. Crit. Care Med., December 1, 2007; 176(11): 1098 - 1107.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
C. K. Haston, M. Begin, G. Dorion, and S. M. Cory
Distinct Loci Influence Radiation-Induced Alveolitis from Fibrosing Alveolitis in the Mouse
Cancer Res., November 15, 2007; 67(22): 10796 - 10803.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2007 by the American Society for Investigative Pathology.