Metalloelastase is required for macrophage-mediated proteolysis and matrix invasion in mice

J. Michael Shipley, Robin L. Wesselschmidt, Dale K. Kobayashi, Timothy J. Ley, Steven D. Shapiro

Research output: Contribution to journalArticlepeer-review

397 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)3942-3946
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number9
DOIs
StatePublished - Apr 30 1996

Keywords

  • basement membrane
  • elastin
  • targeted gene disruption

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