AJP - Lung Ad Instruments
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Lung Cell Mol Physiol 281: L868-L878, 2001;
1040-0605/01 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (19)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Zhu, Y. K.
Right arrow Articles by Rennard, S. I.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zhu, Y. K.
Right arrow Articles by Rennard, S. I.
Vol. 281, Issue 4, L868-L878, October 2001

Synergistic neutrophil elastase-cytokine interaction degrades collagen in three-dimensional culture

Y. K. Zhu1, X. D. Liu2, C. M. Sköld3, T. Umino2, H. J. Wang2, J. R. Spurzem2, T. Kohyama2, R. F. Ertl2, and S. I. Rennard2

1 Jincheng Hospital, Lanzhou 730050, China; 2 University of Nebraska Medical Center, Omaha, Nebraska 68198-5125; and 3 Karolinska Institute, S-171 76 Stockholm, Sweden

Proteolytic degradation of extracellular matrix is thought to play an important role in many lung disorders. In the current study, human lung fibroblasts were cast into type I collagen gels and floated in medium containing elastase, cytomix (combination of tumor necrosis factor-alpha , interleukin-1beta , and interferon-gamma ), or both. After 5 days, gel collagen content was determined by measuring hydroxyproline. Elastase alone did not result in collagen degradation, but in the presence of fibroblasts, elastase reduced hydroxyproline content to 75.2% (P < 0.01), whereas cytomix alone resulted in reduction of hydroxyproline content to 93% (P < 0.05). The combination of elastase and cytomix reduced hydroxyproline content to 5.2% (P < 0.01). alpha 1-Proteinase inhibitor blocked this synergy. Gelatin zymography and Western blot revealed that matrix metalloproteinase (MMP)-1, -3, and -9 were induced by cytomix and activated in the presence of elastase. Tissue inhibitor of metalloproteinase (TIMP)-1 and -2 were also induced by cytomix but were cleaved by elastase. We conclude that a synergistic interaction between cytomix and elastase, mediated through cytokine induction of MMP production and elastase-induced activation of latent MMPs and degradation of TIMPs, can result in a dramatic augmentation of collagen degradation. These findings support the notion that interaction among inflammatory mediators secreted by mononuclear cells and neutrophils can induce tissue cells to degrade extracellular matrix. Such a mechanism may contribute to the protease-anti-protease imbalance in emphysema.

matrix metalloproteinases; collagen; fibroblasts; interleukin-1; tumor necrosis factor


This article has been cited by other articles:


Home page
 Am. J. Respir. Crit. Care Med.Home page
S. Togo, O. Holz, X. Liu, H. Sugiura, K. Kamio, X. Wang, S. Kawasaki, Y. Ahn, K. Fredriksson, C. M. Skold, et al.
Lung Fibroblast Repair Functions in Patients with Chronic Obstructive Pulmonary Disease Are Altered by Multiple Mechanisms
Am. J. Respir. Crit. Care Med., August 1, 2008; 178(3): 248 - 260.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
W. Ning, Y. Dong, J. Sun, C. Li, M. A. Matthay, C. A. Feghali-Bostwick, and A. M. K. Choi
Cigarette Smoke Stimulates Matrix Metalloproteinase-2 Activity via EGR-1 in Human Lung Fibroblasts
Am. J. Respir. Cell Mol. Biol., April 1, 2007; 36(4): 480 - 490.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
K. Fredriksson, X. D. Liu, J. Lundahl, J. Klominek, S. I. Rennard, and C. M. Skold
Red blood cells increase secretion of matrix metalloproteinases from human lung fibroblasts in vitro
Am J Physiol Lung Cell Mol Physiol, February 1, 2006; 290(2): L326 - L333.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
P. J. Barnes and R. A. Stockley
COPD: current therapeutic interventions and future approaches
Eur. Respir. J., June 1, 2005; 25(6): 1084 - 1106.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
W. B. Saunders, K. J. Bayless, and G. E. Davis
MMP-1 activation by serine proteases and MMP-10 induces human capillary tubular network collapse and regression in 3D collagen matrices
J. Cell Sci., May 15, 2005; 118(10): 2325 - 2340.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
A. Linden, M. Laan, and G. P. Anderson
Neutrophils, interleukin-17A and lung disease
Eur. Respir. J., January 1, 2005; 25(1): 159 - 172.
[Abstract] [Full Text] [PDF]

Home page
 ChestHome page
J. H. J. Vernooy, J. H. N. Lindeman, J. A. Jacobs, R. Hanemaaijer, and E. F. M. Wouters
Increased Activity of Matrix Metalloproteinase-8 and Matrix Metalloproteinase-9 in Induced Sputum From Patients With COPD
Chest, December 1, 2004; 126(6): 1802 - 1810.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
E{-}J.D. Oudijk, J{-}W.J. Lammers, and L. Koenderman
Systemic inflammation in chronic obstructive pulmonary disease
Eur. Respir. J., November 2, 2003; 22(46_suppl): 5s - 13s.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
J. J. Atkinson and R. M. Senior
Matrix Metalloproteinase-9 in Lung Remodeling
Am. J. Respir. Cell Mol. Biol., January 1, 2003; 28(1): 12 - 24.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
T. Kohyama, X. Liu, Y. K. Zhu, F.-Q. Wen, H. J. Wang, Q. Fang, T. Kobayashi, and S. I. Rennard
Phosphodiesterase 4 Inhibitor Cilomilast Inhibits Fibroblast-Mediated Collagen Gel Degradation Induced by Tumor Necrosis Factor-{alpha} and Neutrophil Elastase
Am. J. Respir. Cell Mol. Biol., October 1, 2002; 27(4): 487 - 494.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online