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Membrane-bound FRET probe visualizes MMP12 activity in pulmonary inflammation

Nature Chemical Biology volume 5, pages 628–630 (2009)Cite this article

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.

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Figure 1: FRET-based reporters of the LaRee series.
Figure 2: MMP12 activity on cultured and native macrophages measured with LaRee1.

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Acknowledgements

We thank M. Gutierrez (EMBL) for RAW 264.7 macrophages, O. Gallego (EMBL) for liposomes, H. Stichnoth (EMBL) for tissue culture, S. Hirtz for genotyping, S. Schubert for discussions and mouse work and J.R. Harkema (Michigan State University) for providing particulate matter (PM10). This work was supported in part by grants from the European Union (LSHG-CT-2003-503259 to C.S. and MEXT-2004-013666 to M.A.M.).

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Author notes

  1. Marcus A Mall and Carsten Schultz: These authors contributed equally to this work.

Authors and Affiliations

  1. Cell Biology and Biophysics Unit, European Molecular Biology Laboratory, Heidelberg, Germany

    Amanda Cobos-Correa & Carsten Schultz

  2. Molecular Medicine Partnership Unit, European Molecular Biology Laboratory and University of Heidelberg, Heidelberg, Germany

    Amanda Cobos-Correa, Stefanie Diemer, Marcus A Mall & Carsten Schultz

  3. Department of Pediatrics III, Pediatric Pulmonology and Cystic Fibrosis Center, University of Heidelberg, Heidelberg, Germany

    Johanna B Trojanek & Stefanie Diemer

Authors
  1. Amanda Cobos-Correa
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  2. Johanna B Trojanek
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  3. Stefanie Diemer
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  4. Marcus A Mall
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  5. Carsten Schultz
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Contributions

A.C.-C., M.A.M. and C.S. designed the experiments and wrote the manuscript. A.C.-C. performed experiments and analyzed data, and J.B.T. and S.D. performed animal experiments.

Corresponding authors

Correspondence to Marcus A Mall or Carsten Schultz.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–9 and Supplementary Methods (PDF 732 kb)

Supplementary Movie 1

Unstimulated macrophages do not show pericellular MMP12 activity as measured with LaRee1. (AVI 23044 kb)

Supplementary Movie 2

Real time imaging of MMP12 activity at the surface of LPSstimulated macrophages measured with LaRee1. (AVI 23812 kb)

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Cobos-Correa, A., Trojanek, J., Diemer, S. et al. Membrane-bound FRET probe visualizes MMP12 activity in pulmonary inflammation. Nat Chem Biol 5, 628–630 (2009). https://doi.org/10.1038/nchembio.196

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  • DOI: https://doi.org/10.1038/nchembio.196

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