Membrane-bound FRET probe visualizes MMP12 activity in pulmonary inflammation

Nat Chem Biol. 2009 Sep;5(9):628-30. doi: 10.1038/nchembio.196. Epub 2009 Aug 2.

Abstract

MMP12 is a metalloproteinase implicated in inflammation. To monitor its activity, we synthesized a membrane-targeted reporter (LaRee1) based on Foerster resonance energy transfer (FRET). Unlike existing sensors, LaRee1 detects MMP12 activity by loss of FRET plus internalization of the lipidated fragment. In bronchoalveolar lavages from a mouse model of pulmonary inflammation, LaRee1 detected MMP12 activity at the surface of activated macrophages. LaRee1 may become a powerful tool for monitoring lung disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bronchoalveolar Lavage Fluid / chemistry
  • Cell Line
  • Cell Membrane / enzymology*
  • Fluorescence Resonance Energy Transfer / methods*
  • Fluorescent Dyes
  • Macrophages, Alveolar / enzymology
  • Matrix Metalloproteinase 12 / genetics
  • Matrix Metalloproteinase 12 / metabolism*
  • Mice
  • Mice, Knockout
  • Microscopy, Confocal
  • Peptides / chemical synthesis
  • Peptides / chemistry
  • Peptides / metabolism
  • Pneumonia / enzymology*
  • Recombinant Proteins / metabolism

Substances

  • Fluorescent Dyes
  • Peptides
  • Recombinant Proteins
  • Matrix Metalloproteinase 12