Membrane-bound FRET probe visualizes MMP12 activity in pulmonary inflammation (original) (raw)

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.

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Figure 2: MMP12 activity on cultured and native macrophages measured with LaRee1.

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References

  1. Shapiro, S.D., Kobayashi, D.K. & Ley, T.J. J. Biol. Chem. 268, 23824–23829 (1993).
    CAS PubMed Google Scholar
  2. Churg, A. et al. Am. J. Respir. Crit. Care Med. 167, 1083–1089 (2003).
    Article Google Scholar
  3. Hautamaki, R.D., Kobayashi, D.K., Senior, R.M. & Shapiro, S.D. Science 277, 2002–2004 (1997).
    Article CAS Google Scholar
  4. Morris, D.G. et al. Nature 422, 169–173 (2003).
    Article CAS Google Scholar
  5. Vos, C.M.P., van Haastert, E.S., de Groot, C.J.A., van der Valk, P. & de Vries, H.E. J. Neuroimmunol. 138, 106–114 (2003).
    Article CAS Google Scholar
  6. Johnson, J.L., George, S.J., Newby, A.C. & Jackson, C.L. Proc. Natl. Acad. Sci. USA 102, 15575–15580 (2005).
    Article CAS Google Scholar
  7. Hu, J.L., Van den Steen, P.E., Sang, Q.X.A. & Opdenakker, G. Nat. Rev. Drug Discov. 6, 480–498 (2007).
    Article CAS Google Scholar
  8. Turk, B. Nat. Rev. Drug Discov. 5, 785–799 (2006).
    Article CAS Google Scholar
  9. Lombard, C., Saulnier, J. & Wallach, J. Biochimie 87, 265–272 (2005).
    Article CAS Google Scholar
  10. Jiang, T. et al. Proc. Natl. Acad. Sci. USA 101, 17867–17872 (2004).
    Article CAS Google Scholar
  11. Bremer, C., Tung, C.H. & Weissleder, R. Nat. Med. 7, 743–748 (2001).
    Article CAS Google Scholar
  12. Ouyang, M.X. et al. J. Biol. Chem. 283, 17740–17748 (2008).
    Article CAS Google Scholar
  13. Yang, J. et al. Biochim. Biophys. Acta 1773, 400–407 (2007).
    Article CAS Google Scholar
  14. Devel, L. et al. J. Biol. Chem. 281, 11152–11160 (2006).
    Article CAS Google Scholar
  15. Döring, G. Am. J. Respir. Crit. Care Med. 150, S114–S117 (1994).
    Article Google Scholar
  16. Gaggar, A. et al. Am. J. Physiol. Lung Cell. Mol. Physiol. 293, L96–L104 (2007).
    Article CAS Google Scholar
  17. Lanone, S. et al. J. Clin. Invest. 110, 463–474 (2002).
    Article CAS Google Scholar
  18. Belaaouaj, A. et al. J. Biol. Chem. 270, 14568–14575 (1995).
    Article CAS Google Scholar
  19. Bachoual, R. et al. Chem. Res. Toxicol. 20, 1426–1433 (2007).
    Article CAS Google Scholar
  20. Mutlu, G.M. et al. J. Clin. Invest. 117, 2952–2961 (2007).
    Article CAS Google Scholar
  21. Churg, A. et al. Am. J. Respir. Cell Mol. Biol. 27, 368–374 (2002).
    Article CAS Google Scholar

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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
  2. Johanna B Trojanek
  3. Stefanie Diemer
  4. Marcus A Mall
  5. Carsten Schultz

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 toMarcus A Mall or Carsten Schultz.

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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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