Report

Inflammation Dampened by Gelatinase A Cleavage of Monocyte Chemoattractant Protein-3

See allHide authors and affiliations

Science  18 Aug 2000:
Vol. 289, Issue 5482, pp. 1202-1206
DOI: 10.1126/science.289.5482.1202

You are currently viewing the abstract.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

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.

  • * To whom correspondence should be addressed. E-mail: overall{at}interchange.ubc.ca

View Full Text

Stay Connected to Science