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

• DOI: 10.1126/science.289.5482.1202
• Publication Date: 2002-07-27T09:50:55Z
• Authors: G. Angus McQuibban; Jiang-Hong Gong; Eric M. Tam; Christopher A. G....; Ian Clark-Lewis; Christopher M. Ov...
• Keywords: Hemopexin; Monocyte; Gelatinase A; CXC chemokine receptors; CXCL2

Tissue degradation by the matrix metalloproteinase gelatinase A is pivotal to inflammation and metastases. Recognizing catalytic importance of substrate-binding exosites outside domain, we screened for extracellular substrates using hemopexin domain as bait in yeast two-hybrid system. Monocyte chemoattractant protein–3 (MCP-3) was identified a physiological substrate A. Cleaved MCP-3 binds CC-chemokine receptors–1, –2, –3, but no longer induces calcium fluxes or promotes chemotaxis, instead acts general chemokine antagonist that dampens inflammation. This suggests metalloproteinases are both effectors regulators inflammatory response.