A fluorescent probe for the detection of myeloperoxidase activity in atherosclerosis-associated macrophages

Joanna Shepherd1, Scott A Hilderbrand, Peter Waterman

  • 1Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA.

Chemistry & Biology
|November 21, 2007
PubMed

Insights

A new imaging probe, sulfonaphthoaminophenyl fluorescein (SNAPF), can detect hypochlorous acid (HOCl) produced by inflammatory cells. This tool visualizes HOCl in animal models and human arteries, aiding atherosclerosis research.

Area of Science:

  • Biomedical imaging
  • Molecular imaging
  • Inflammation research

Background:

  • Myeloperoxidase (MPO)-derived hypochlorous acid (HOCl) contributes to atherosclerosis and inflammatory diseases.
  • Existing methods for HOCl detection are limited in vivo.

Purpose of the Study:

  • To develop and validate a novel imaging probe, SNAPF, for selective detection of HOCl.
  • To assess the utility of SNAPF for in vivo imaging of HOCl production in inflammatory conditions.

Main Methods:

  • Synthesis of sulfonaphthoaminophenyl fluorescein (SNAPF) probe.
  • Detection of HOCl in stimulated MPO-expressing cells and bone marrow-derived macrophages.
  • In vivo imaging of HOCl production in experimental murine peritonitis.
  • Detection of HOCl in human atherosclerotic arteries using fluorescence reflectance imaging.

Main Results:

  • SNAPF selectively reacts with HOCl.
  • SNAPF successfully detected HOCl produced by MPO-expressing cells in vitro.
  • In vivo studies demonstrated HOCl production by neutrophils in murine peritonitis.
  • HOCl production by MPO-expressing cells was visualized in human atherosclerotic arteries.

Conclusions:

  • SNAPF is a valuable tool for detecting HOCl produced by MPO-expressing cells.
  • Fluorescence reflectance imaging with SNAPF enables noninvasive molecular imaging of HOCl in vivo.
  • This approach can help implicate HOCl and MPO in inflammatory tissue damage, particularly in atherosclerosis.

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