Non-invasive In Vivo Fluorescence Optical Imaging of Inflammatory MMP Activity Using an Activatable Fluorescent Imaging Agent.
Non-invasive In Vivo Fluorescence Optical Imaging of Inflammatory MMP Activity Using an Activatable Fluorescent Imaging Agent.
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DOI：
10.3791/55180
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发表时间：
2017-05
期刊：
影响因子：
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通讯作者：
J. Schwenck;F. Maier;M. Kneilling;S. Wiehr;K. Fuchs
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文献类型：
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作者：
J. Schwenck;F. Maier;M. Kneilling;S. Wiehr;K. Fuchs
本文描述了一种非侵入性的方法成像基质金属蛋白酶（MMP）活性的可激活的荧光探针，通过在体内荧光光学成像（OI），在两种不同的小鼠模型的炎症：类风湿性关节炎（RA）和接触性超敏反应（OHSS）模型。与低于650 nm的波长相比，具有近红外（NIR）窗口（650 - 950 nm）中的波长的光允许更深的组织穿透和最小的信号吸收。使用荧光OI的主要优点是它便宜、快速且易于在不同的动物模型中实施。可激活的荧光探针在其失活状态下是光学沉默的，但当被蛋白酶激活时变得高度荧光。活化的MMPs导致组织破坏，并在迟发型超敏反应（DTHR）如RA和CHR中的疾病进展中起重要作用。此外，MMPs是软骨和骨降解的关键蛋白酶，并且由巨噬细胞、成纤维细胞和软骨细胞响应促炎细胞因子而诱导。在这里，我们使用由关键MMP如MMP-2、-3、-9和-13激活的探针，并描述了疾病诱导后6天RA和对照小鼠以及右耳急性（1x激发）和慢性（5x激发）耳鸣小鼠中MMP活性的近红外荧光OI成像方案，与健康耳朵相比。
This paper describes a non-invasive method for imaging matrix metalloproteinases (MMP)-activity by an activatable fluorescent probe, via in vivo fluorescence optical imaging (OI), in two different mouse models of inflammation: a rheumatoid arthritis (RA) and a contact hypersensitivity reaction (CHR) model. Light with a wavelength in the near infrared (NIR) window (650 - 950 nm) allows a deeper tissue penetration and minimal signal absorption compared to wavelengths below 650 nm. The major advantages using fluorescence OI is that it is cheap, fast and easy to implement in different animal models. Activatable fluorescent probes are optically silent in their inactivated states, but become highly fluorescent when activated by a protease. Activated MMPs lead to tissue destruction and play an important role for disease progression in delayed-type hypersensitivity reactions (DTHRs) such as RA and CHR. Furthermore, MMPs are the key proteases for cartilage and bone degradation and are induced by macrophages, fibroblasts and chondrocytes in response to pro-inflammatory cytokines. Here we use a probe that is activated by the key MMPs like MMP-2, -3, -9 and -13 and describe an imaging protocol for near infrared fluorescence OI of MMP activity in RA and control mice 6 days after disease induction as well as in mice with acute (1x challenge) and chronic (5x challenge) CHR on the right ear compared to healthy ears.