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Metalloelastase is required for macrophage-mediated proteolysis and matrix invasion in mice
J M Shipley1, R L Wesselschmidt, D K Kobayashi
1Division of Respiratory and Critical Care, Washington University School of Medicine, Jewish Hospital, St. Louis, MO 63110, USA.
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.
Insights
Macrophage metalloelastase (MME) is crucial for breaking down the extracellular matrix and enabling tissue invasion by macrophages during inflammation. MME-deficient mice show significantly reduced matrix degradation and impaired macrophage invasion capabilities.
Area of Science:
- Immunology
- Molecular Biology
- Biochemistry
Background:
- Macrophages play a key role in tissue remodeling during inflammation by secreting proteinases.
- The specific contribution of macrophage metalloelastase (MME) to these processes is not fully understood.
Purpose of the Study:
- To investigate the role of macrophage metalloelastase (MME) in macrophage-mediated extracellular matrix proteolysis and tissue invasion.
- To determine the necessity of MME for macrophage function in inflammatory contexts.
Main Methods:
- Gene targeting was used to create MME-deficient (MME-/-) mice.
- Macrophage-mediated degradation of extracellular matrix components was assessed.
- Macrophage penetration of reconstituted basement membranes in vitro and in vivo was evaluated.
Main Results:
- Macrophages from MME-/- mice exhibited a significantly reduced ability to degrade extracellular matrix components.
- MME-/- macrophages demonstrated a near-complete inability to penetrate reconstituted basement membranes.
- These findings highlight the critical role of MME in macrophage proteolytic activity.
Conclusions:
- Macrophage metalloelastase (MME) is essential for extracellular matrix proteolysis mediated by macrophages.
- MME is indispensable for macrophage tissue invasion, impacting inflammatory processes.