help button home button
AJRCCM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Published ahead of print on December 4, 2002, doi:10.1164/rccm.200209-1007OC

Am. J. Respir. Crit. Care Med., Volume 167, Number 6, March 2003, 925-932

A more recent version of this article appeared on March 15, 2003
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
200209-1007OCv1
167/6/925    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
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 Pardo, A.
Right arrow Articles by Selman, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pardo, A.
Right arrow Articles by Selman, M.

Submitted on September 11, 2002
Accepted on November 27, 2002

BLEOMYCIN-INDUCED PULMONARY FIBROSIS IS ATTENUATED IN GAMMA-GLUTAMYL TRANSPEPTIDASE-DEFICIENT MICE

Annie Pardo1, Victor Ruiz2, Jose Luis Arreola2, Remedios Ramirez1, Jose Cisneros-Lira3, Miguel Gaxiola2, Roberto Barrios4, Kala V Subbarao4, Michael W Lieberman4, and Moises Selman2*

1 Facultad de Ciencias, Universidad Nacional Autonoma de Mexico, Mexico, DF, Mexico, 2 Unidad de Investigacion, Instituto Nacional de Enfermedades Respiratorias, Mexico, DF, Mexico, 3 Unidad de Investigacion, Instituto Nacional de Enfermedades Respiratorias, Mexico, DF, Mexico; Facultad de Ciencias, Universidad Nacional Autonoma de Mexico, Mexico, DF, Mexico, 4 Department of Pathology, Baylor College of Medicine, Houston, Texas, USA

* To whom correspondence should be addressed. E-mail: mselman{at}sni.conacyt.mx.

To investigate repair mechanisms in bleomycin-induced pulmonary fibrosis, we used mice deficient in {gamma}glutamyl transpeptidase (GGT-/-), a key enzyme in GSH and cysteine metabolism. Seventy-two hours after bleomycin (0.03 U/g), GGT-/- mice displayed a different inflammatory response to wild-type as judged by a near absence of neutrophils in lung tissue and bronchoalveolar lavage and a less-pronounced rise in MMP-9. Inflammation in GGT-/- consisted mainly of lymphocytes and macrophages. At one month, lungs from bleomycin-treated GGT-/- exhibited minimal areas of fibrosis compared to wild-type (light microscopy fibrosis index: 510±756 versus 1975±817, p<0.01). Lung collagen content revealed a significant increase in bleomycin-treated wild-type (15.1±3.8 versus 8.5±0.7 µg OH-proline/mg dry weight; p<0.01), but not in GGT-/- (10.4±1.7 versus 8.8±0.8). Control lungs from GGT-/- showed a significant reduction of cysteine (0.03±0.005 versus 0.055±0.001, P<0.02) and GSH levels (1.24±0.055 versus 1.79±0.065, P<0.002). These values decreased after 72h of bleomycin in both GGT-/- and wild-type but reached their respective control values after one month. Supplementation with N-acetyl cysteine partially ameliorated the effects of GGT-deficiency. These findings suggest that increased neutrophils and MMP-9 during the early inflammatory response and adequate thiol reserves are key elements in the fibrotic response following bleomycin-induced pulmonary injury.
Key words: GSH, MMP-9, neutrophils, cysteine




This article has been cited by other articles:


Home page
 J. Nutr.Home page
J. N. Baumgardner, K. Shankar, L. Hennings, E. Albano, T. M. Badger, and M. J. J. Ronis
N-Acetylcysteine Attenuates Progression of Liver Pathology in a Rat Model of Nonalcoholic Steatohepatitis
J. Nutr., October 1, 2008; 138(10): 1872 - 1879.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
H. R. Collard, B. B. Moore, K. R. Flaherty, K. K. Brown, R. J. Kaner, T. E. King Jr., J. A. Lasky, J. E. Loyd, I. Noth, M. A. Olman, et al.
Acute Exacerbations of Idiopathic Pulmonary Fibrosis
Am. J. Respir. Crit. Care Med., October 1, 2007; 176(7): 636 - 643.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
D. Kass, R. S. Bridges, A. Borczuk, and S. Greenberg
Methionine Aminopeptidase-2 as a Selective Target of Myofibroblasts in Pulmonary Fibrosis
Am. J. Respir. Cell Mol. Biol., August 1, 2007; 37(2): 193 - 201.
[Abstract] [Full Text] [PDF]

Home page
 Proc Am Thorac SocHome page
A. Pardo and M. Selman
Matrix metalloproteases in aberrant fibrotic tissue remodeling.
Proceedings of the ATS, January 1, 2006; 3(4): 383 - 388.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
P. Bonniaud, P. J. Margetts, M. Kolb, J. A. Schroeder, A. M. Kapoun, D. Damm, A. Murphy, S. Chakravarty, S. Dugar, L. Higgins, et al.
Progressive Transforming Growth Factor {beta}1-induced Lung Fibrosis Is Blocked by an Orally Active ALK5 Kinase Inhibitor
Am. J. Respir. Crit. Care Med., April 15, 2005; 171(8): 889 - 898.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
W. E. Lawson, V. V. Polosukhin, O. Zoia, G. T. Stathopoulos, W. Han, D. Plieth, J. E. Loyd, E. G. Neilson, and T. S. Blackwell
Characterization of Fibroblast-specific Protein 1 in Pulmonary Fibrosis
Am. J. Respir. Crit. Care Med., April 15, 2005; 171(8): 899 - 907.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
M. J. Tobin
Tuberculosis, Lung Infections, Interstitial Lung Disease, Social Issues and Journalology in AJRCCM 2003
Am. J. Respir. Crit. Care Med., January 15, 2004; 169(2): 288 - 300.
[Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
J. Cisneros-Lira, M. Gaxiola, C. Ramos, M. Selman, and A. Pardo
Cigarette smoke exposure potentiates bleomycin-induced lung fibrosis in guinea pigs
Am J Physiol Lung Cell Mol Physiol, October 1, 2003; 285(4): L949 - L956.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Proc. Am. Thorac. Soc. Am. J. Respir. Cell Mol. Biol.
Copyright © 2002 American Thoracic Society