A novel fluorescent probe for the detection of myeloperoxidase activity in atherosclerosis-associated macrophages
A novel fluorescent probe for the detection of myeloperoxidase activity in atherosclerosis-associated macrophages
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发表时间：
2009
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通讯作者：
J. Shepherd;S. Hilderbrand;P. Waterman;J. Heinecke;Ralph Weissleder;P. Libby;±. JoannaShepherd
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作者：
J. Shepherd;S. Hilderbrand;P. Waterman;J. Heinecke;Ralph Weissleder;P. Libby;±. JoannaShepherd
髓过氧化物酶（MPO）衍生的氧化剂次氯酸（HOCl/OCl −）与动脉粥样硬化和其他炎症状态的发病机制有关。我们已经合成了一种新的成像探针，磺基萘并氨基苯基荧光素（SNAPF），选择性地反应HOCl。SNAPF检测由从人全血培养的受刺激的MPO表达细胞产生的HOCl，以及来自从表达人MPO的转基因小鼠分离的骨髓（BM）衍生的巨噬细胞的HOCl。两条线的证据表明，SNAPF允许在体内成像的HOCl生产。首先，我们使用这种方法来证明实验性小鼠腹膜炎中中性粒细胞产生HOCl。其次，我们检测了人动脉粥样硬化动脉中MPO表达细胞的HOCl产生。因此，通过SNAPF的荧光反射成像可以提供一种有价值的非侵入性分子成像工具，用于在发炎组织的损伤中暗示HOCl和MPO。
SUMMARY The myeloperoxidase (MPO)-derived oxidant hypochlorous acid (HOCl/OCl − ) is implicated in the pathogenesis of atherosclerosis and other inflammatory states. We have synthesized a novel imaging probe, sulfonaphthoaminophenyl fluorescein (SNAPF), that selectively reacts to 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 non-invasive molecular imaging tool for implicating HOCl and MPO in the damage of inflamed tissues.