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

J. Biol. Chem., Vol. 280, Issue 34, 30201-30205, August 26, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/34/30201    most recent M503292200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kassim, S. Y. Articles by Heinecke, J. W. Search for Related Content PubMed PubMed Citation Articles by Kassim, S. Y. Articles by Heinecke, J. W. Social Bookmarking                      What's this?

NADPH Oxidase Restrains the Matrix Metalloproteinase Activity of Macrophages^*

Sean Y. Kassim, Xiaoyun Fu, W. Conrad Liles, Steven D. Shapiro¶, William C. Parks||, and Jay W. Heinecke**

From the Department of Medicine, University of Washington, Seattle, Washington 98195, the Departments of Medicine and ^||Pediatrics, Washington University, St. Louis, Missouri 63110, and the ^¶Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115

Matrix metalloproteinases (MMPs) regulate numerous functions in normal and disease processes; thus, irreversibly blocking their activity is a key step in regulating MMP catalysis. We previously showed in vitro that oxidizing intermediates generated by phagocytes inactivate MMPs by modifying specific amino acids. To assess whether this mechanism operates in vivo, we focused on MMP-12, a macrophage-specific MMP known to mediate emphysema in mouse models. We found that mice lacking gp91^phox, a phagocyte-specific component of the NADPH oxidase, developed extensive, spontaneous emphysematous destruction of their peripheral air spaces, whereas mice deficient in both NADPH oxidase and MMP-12 were protected from spontaneous emphysema. Although gp91^phox-null and wild-type macrophages produced equivalent levels of MMP-12 protein, the oxidant-deficient cells had greater MMP-12 activity than wild-type macrophages. These findings indicate that reactive intermediates provide a physiological mechanism to protect tissues from excessive macrophage-mediated damage during inflammation.

Received for publication, March 25, 2005 , and in revised form, June 3, 2005.

^* This work was supported by National Institutes of Health Grants HL078527, HL075381, AG021191, HL64344, HL62995, HL77555, P01-HL29594, P30-ES07033, and P50-HL073996 and by the Donald W. Reynolds Foundation. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^** To whom correspondence should be addressed: Division of Metabolism, Endocrinology, and Nutrition, Box 356426, University of Washington, Seattle, WA 98195. E-mail: heinecke{at}u.washington.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				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]

				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]

				L. A. Ridnour, A. N. Windhausen, J. S. Isenberg, N. Yeung, D. D. Thomas, M. P. Vitek, D. D. Roberts, and D. A. Wink Nitric oxide regulates matrix metalloproteinase-9 activity by guanylyl-cyclase-dependent and -independent pathways PNAS, October 23, 2007; 104(43): 16898 - 16903. [Abstract] [Full Text] [PDF]

				E. L. Martin, T. A. Sheikh, K. J. Leco, J. F. Lewis, and R. A. W. Veldhuizen Contribution of alveolar macrophages to the response of the TIMP-3 null lung during a septic insult Am J Physiol Lung Cell Mol Physiol, September 1, 2007; 293(3): L779 - L789. [Abstract] [Full Text] [PDF]

				K. Bedard and K.-H. Krause The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology Physiol Rev, January 1, 2007; 87(1): 245 - 313. [Abstract] [Full Text] [PDF]