METALLOELASTASE IS REQUIRED FOR MACROPHAGE-MEDIATED PROTEOLYSIS AND MATRIX INVASION IN MICE

Macrophages secrete a variety of proteinases that are thought to parti cipate in remodeling of the extracellular matrix associated with infla mmatory processes. We have eliminated expression of the macrophage met alloelastase (MME) gene by targeted disruption to assess the role of t his protein in macrophage-mediated proteolysis. We found that the macr ophages of MME-deficient (MME -/-) mice have a markedly diminished cap acity to degrade extracellular matrix components. In addition, MME -/- macrophages are essentially unable to penetrate reconstituted basemen t membranes in vitro and in vivo. MME is therefore required for macrop hage-mediated extracellular matrix proteolysis and tissue invasion.