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 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.
Shipley
J M
JM
Division of Respiratory and Critical Care, Washington University School of Medicine, Jewish Hospital, St. Louis, MO 63110, USA.
Wesselschmidt
R L
RL
Kobayashi
D K
DK
Ley
T J
TJ
Shapiro
S D
SD
D000818:Animals; D001483:Base Sequence; D001485:Basement Membrane / Q000502:physiology; D003001:Cloning, Molecular; D017931:DNA Primers; D004549:Elastin / Q000378:metabolism*; D005109:Extracellular Matrix / Q000502:physiology*; D015723:Gene Library; D007249:Inflammation; D017737:Macrophages, Peritoneal / Q000502:physiology*; D053508:Matrix Metalloproteinase 12; D008666:Metalloendopeptidases / Q000096:biosynthesis / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection
D017931:DNA Primers; D011994:Recombinant Proteins; D004549:Elastin; D008666:Metalloendopeptidases; D053508:Matrix Metalloproteinase 12