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

Abstract

The myeloperoxidase (MPO)-derived oxidant hypochlorous acid (HOCI/OCI-) is implicated in the pathogenesis of atherosclerosis and other inflammatory states. We have synthesized an imaging probe, sulfonaphthoamino-phenyl fluorescein (SNAPF), that selectively reacts with HOCI. SNAPF detects HOCI produced by stimulated MPO-expressing cells cultured from human whole blood, as well as HOCI 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 HOCI production. First, we used this approach to demonstrate HOCI production by neutrophils in experimental murine peritonitis. Second, we detected HOCI 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 HOCI and MPO in the damage of inflamed tissues.