References
Query Results -- Details
MGI Accession ID: MGI:3590423
J Number: J:101039
Other Accession IDs:
Title: NADPH oxidase restrains the matrix metalloproteinase activity of macrophages.
Authors: Kassim SY; Fu X; Liles WC; Shapiro SD; Parks WC; Heinecke JW
Journal: J Biol Chem
Volume: 280
Issue: 34
Date: 2005 Aug 26
Year: 2005
Pages: 30201-5
Review Status: Peer Reviewed
Abstract:
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.
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