Inflammation Dampened by Gelatinase A Cleavage of Monocyte Chemoattractant Protein-3
Abstract
Tissue degradation by the matrix metalloproteinase gelatinase A is pivotal to inflammation and metastases. Recognizing the catalytic importance of substrate-binding exosites outside the catalytic domain, we screened for extracellular substrates using the gelatinase A hemopexin domain as bait in the yeast two-hybrid system. Monocyte chemoattractant protein-3 (MCP-3) was identified as a physiological substrate of gelatinase A. Cleaved MCP-3 binds to CC-chemokine receptors-1, -2, and -3, but no longer induces calcium fluxes or promotes chemotaxis, and instead acts as a general chemokine antagonist that dampens inflammation. This suggests that matrix metalloproteinases are both effectors and regulators of the inflammatory response.
- Publication:
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Science
- Pub Date:
- August 2000
- DOI:
- 10.1126/science.289.5482.1202
- Bibcode:
- 2000Sci...289.1202M
- Keywords:
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- IMMUNOLOGY