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Noninvasive In Vivo Quantification of Neutrophil Elastase Activity in Acute Experimental Mouse Lung Injury

机译:急性实验性小鼠肺损伤中性粒细胞弹性蛋白酶活性的非侵入性体内定量分析

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摘要

We developed a neutrophil elastase-specific near-infrared fluorescence imaging agent, which, combined with fluorescence molecular tomographic imaging, allowed us to detect and quantify neutrophil elastase activity in vivo, in real time, and noninvasively in an acute model of lung injury (ALI). Significantly higher fluorescent signal was quantified in mice with LPS/fMLP-induced ALI as compared to healthy controls, correlating with increases in the number of bronchoalveolar lavage cells, neutrophils, and elastase activity. The agent was significantly activated ex vivo in lung sections from ALI but not from control mice, and this activation was ablated by the specific inhibitor sivelestat. Treatment with the specific inhibitor sivelestat significantly reduced lung signal in mice with ALI. These results underscore the unique ability of fluorescence molecular imaging to quantify specific molecular processes in vivo, crucial for understanding the mechanisms underlying disease progression and for assessing and monitoring novel pharmacological interventions.
机译:我们开发了一种中性粒细胞弹性蛋白酶特异性近红外荧光成像剂,结合荧光分子层析成像技术,使我们能够在急性肺损伤模型(ALI)中实时,无创地检测和定量体内中性粒细胞弹性蛋白酶活性。 )。与健康对照组相比,LPS / fMLP诱导的ALI小鼠的荧光信号明显更高,这与支气管肺泡灌洗细胞,嗜中性粒细胞和弹性蛋白酶活性的增加有关。该试剂在ALI的肺切片中有离体激活,但没有从对照小鼠中激活,这种激活被特定的抑制剂ilelestat消除。用特异性抑制剂西乐司他治疗可明显降低ALI小鼠的肺信号。这些结果强调了荧光分子成像在体内定量特定分子过程的独特能力,这对于理解疾病进展的机制以及评估和监测新型药理学干预至关重要。

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