HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: 294/6/L1149    most recent 00481.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Foronjy, R. Articles by D'Armiento, J. Search for Related Content PubMed PubMed Citation Articles by Foronjy, R. Articles by D'Armiento, J.

Transgenic expression of matrix metalloproteinase-9 causes adult-onset emphysema in mice associated with the loss of alveolar elastin

¹Columbia University, New York, New York; and ²Keio University, Tokyo, Japan

Submitted 25 November 2007 ; accepted in final form 29 March 2008

Matrix metalloproteinase (MMP)-9 has been consistently identified in the lungs of patients with chronic obstructive pulmonary disease (COPD). However, its role in the development of the disease remains undefined. Mice that specifically express human MMP-9 in their macrophages were generated, and morphometric, biochemical, and histological analyses were conducted on the transgenic and littermate control mice over 1 yr to determine the effect of macrophage MMP-9 expression on emphysema formation and lung matrix content. Lung morphometry was normal in transgenic mice at 2 mo of age (mean linear intercept = 50 ± 3 littermate mice vs. 51 ± 2 transgenic mice). However, after 12 mo of age, the MMP-9 transgenic mice developed significant air space enlargement (mean linear intercept = 53 ± 3 littermate mice vs. 61 ± 2 MMP-9 transgenic mice; P < 0.04). Lung hydroxyproline content was not significantly different between wild-type and transgenic mice, but MMP-9 did significantly decrease alveolar wall elastin at 1 yr of age (4.9 ± 0.3% area of alveolar wall in the littermate mice vs. 3.3 ± 0.3% area of alveolar wall in the MMP-9 mice; P < 0.004). Thus these results establish a central role for MMP-9 in the pathogenesis of this disease by demonstrating that expression of this protease in macrophages can alter the extracellular matrix and induce progressive air space enlargement in mice.

protease; extracellular matrix; degradation; macrophage

This article has been cited by other articles:

				Y. Nakamaru, C. Vuppusetty, H. Wada, J. C. Milne, M. Ito, C. Rossios, M. Elliot, J. Hogg, S. Kharitonov, H. Goto, et al. A protein deacetylase SIRT1 is a negative regulator of metalloproteinase-9 FASEB J, September 1, 2009; 23(9): 2810 - 2819. [Abstract] [Full Text] [PDF]

				Y. Zhou, A. Mohsenin, E. Morschl, H. W. J. Young, J. G. Molina, W. Ma, C.-X. Sun, H. Martinez-Valdez, and M. R. Blackburn Enhanced Airway Inflammation and Remodeling in Adenosine Deaminase-Deficient Mice Lacking the A2B Adenosine Receptor J. Immunol., June 15, 2009; 182(12): 8037 - 8046. [Abstract] [Full Text] [PDF]

				A. Chetty, G.-J. Cao, M. Severgnini, A. Simon, R. Warburton, and H. C. Nielsen Role of matrix metalloprotease-9 in hyperoxic injury in developing lung Am J Physiol Lung Cell Mol Physiol, October 1, 2008; 295(4): L584 - L592. [Abstract] [Full Text] [PDF]