A fluorescent probe for the detection of myeloperoxidase activity in atherosclerosis-associated macrophages.
The myeloperoxidase (MPO)-derived oxidant hypochlorous acid (HOCl/OCl(-)) is implicated in the pathogenesis of atherosclerosis and other inflammatory states. We have synthesized an imaging probe, sulfonaphthoaminophenyl fluorescein (SNAPF), that selectively reacts with HOCl. SNAPF detects HOCl produced by stimulated MPO-expressing cells cultured from human whole blood, as well as HOCl from bone marrow (BM)-derived macrophages isolated from transgenic mice that express human MPO. Two lines of evidence indicate that SNAPF permits the in vivo imaging of HOCl production. First, we used this approach to demonstrate HOCl production by neutrophils in experimental murine peritonitis. Second, we detected HOCl production by MPO expressing cells in human atherosclerotic arteries. Thus, fluorescence reflectance imaging by SNAPF may provide a valuable noninvasive molecular imaging tool for implicating HOCl and MPO in the damage of inflamed tissues.
Shepherd
Joanna
J
Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA.
Hilderbrand
Scott A
SA
Waterman
Peter
P
Heinecke
Jay W
JW
Weissleder
Ralph
R
Libby
Peter
P
D000818:Animals; D050197:Atherosclerosis / Q000201:enzymology* / Q000473:pathology; D001483:Base Sequence; D017931:DNA Primers; D005456:Fluorescent Dyes; D006801:Humans; D008264:Macrophages / Q000201:enzymology*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D009195:Peroxidase / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D021241:Spectrometry, Mass, Electrospray Ionization
D017931:DNA Primers; D005456:Fluorescent Dyes; D009195:Peroxidase