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Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/13816
Título

Macrophage elastase kills bacteria within murine macrophages

AutorHoughton, A. McGarry; Hartzell, William O.; Robbins, Clinton S.; Gomis-Rüth, F. Xavier ; Shapiro, Steven D.
Palabras claveMacrophage elastase
Nitric oxide
Reactive oxygen metabolite
Antiinfective agent
MMP12 protein
Bacteria (microorganisms)
Bacterium
Cytology
Murinae
Mus
Negibacteria
Posibacteria
Defense mechanism
Antimicrobial activity
Fecha de publicación17-jun-2009
EditorNature Publishing Group
CitaciónNature 460(7255): 637-641 (2009)
ResumenMacrophages are aptly positioned to function as the primary line of defence against invading pathogens in many organs, including the lung and peritoneum. Their ability to phagocytose and clear microorganisms has been well documented. Macrophages possess several substances with which they can kill bacteria, including reactive oxygen species, nitric oxide, and antimicrobial proteins. We proposed that macrophage-derived proteinases may contribute to the antimicrobial properties of macrophages. Macrophage elastase (also known as matrix metalloproteinase 12 or MMP12) is an enzyme predominantly expressed in mature tissue macrophages and is implicated in several disease processes, including emphysema. Physiological functions for MMP12 have not been described. Here we show that Mmp12-/- mice exhibit impaired bacterial clearance and increased mortality when challenged with both Gram-negative and Gram-positive bacteria at macrophage-rich portals of entry, such as the peritoneum and lung. Intracellular stores of MMP12 are mobilized to macrophage phagolysosomes after the ingestion of bacterial pathogens. Once inside phagolysosomes, MMP12 adheres to bacterial cell walls where it disrupts cellular membranes resulting in bacterial death. The antimicrobial properties of MMP12 do not reside within its catalytic domain, but rather within the carboxy-terminal domain. This domain contains a unique four amino acid sequence on an exposed β loop of the protein that is required for the observed antimicrobial activity. The present study represents, to our knowledge, the first report of direct antimicrobial activity by a matrix metallopeptidase, and describes a new antimicrobial peptide that is sequentially and structurally unique in nature.
Descripción6 pages, 4 figures.-- PMID: 19536155 [PubMed].-- Article in press.
Versión del editorhttp://dx.doi.org/10.1038/nature08181
URIhttp://hdl.handle.net/10261/13816
DOI10.1038/nature08181
ISSN0028-0836 (Print)
1476-4687 (Online)
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