Metalloelastase is Required for Macrophage-Mediated Proteolysis and Matrix Invasion in Mice

Macrophages secrete a variety of proteinases that are thought to participate in remodeling of the extracellular matrix associated with inflammatory processes. We have eliminated expression of the macrophage metalloelastase (MME) gene by targeted disruption to assess the role of this protein in macro...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1996-04, Vol.93 (9), p.3942-3946
Main Authors: Shipley, J. Michael, Wesselschmidt, Robin L., Kobayashi, Dale K., Ley, Timothy J., Shapiro, Steven D.
Format: Article
Language:English
Subjects:
Animals
Base Sequence
Basement membrane
Basement Membrane - physiology
Biochemistry
Cloning, Molecular
DNA Primers
Elastin - metabolism
Embryonic stem cells
Exons
Extracellular Matrix - physiology
Gene Library
Genes
Genetic mutation
Genomics
Giant cells
Inflammation
Macrophages
Macrophages, Peritoneal - physiology
Matrix Metalloproteinase 12
Membranes
Metalloendopeptidases - biosynthesis
Metalloendopeptidases - metabolism
Mice
Mice, Inbred Strains
Molecular Sequence Data
Peritoneal macrophages
Polymerase Chain Reaction
Proteins
Recombinant Proteins - metabolism
Rodents
Transfection
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Summary:Macrophages secrete a variety of proteinases that are thought to participate in remodeling of the extracellular matrix associated with inflammatory processes. We have eliminated expression of the macrophage metalloelastase (MME) gene by targeted disruption to assess the role of this protein in macrophage-mediated proteolysis. We found that the macrophages of MME-deficient (MME -/-) mice have a markedly diminished capacity to degrade extracellular matrix components. In addition, MME -/- macrophages are essentially unable to penetrate reconstituted basement membranes in vitro and in vivo. MME is therefore required for macrophage-mediated extracellular matrix proteolysis and tissue invasion.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.93.9.3942