Non-Invasive whole-body detection of complement activation using radionuclide imaging in a mouse model of myocardial ischaemia-reperfusion injury.
Non-Invasive whole-body detection of complement activation using radionuclide imaging in a mouse model of myocardial ischaemia-reperfusion injury.
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DOI：
10.1038/s41598-017-16387-1
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发表时间：
2017-11-23
影响因子：
4.6
通讯作者：
Mullen GE
中科院分区：
文献类型：
--
作者：
Sharif-Paghaleh E;Yap ML;Puhl SL;Badar A;Torres JB;Chuamsaamarkkee K;Kampmeier F;Smith RA;Clark J;Blower PJ;Sacks S;Mullen GE
补体激活是公认的心肌缺血再灌注损伤 (IRI) 介质，心肌细胞是补体蛋白（包括核心成分 C3）的已知来源，其激活产物可介导组织炎症、细胞死亡和促纤维化信号传导。我们研究了通过体外成像检测和量化稳定共价结合产物 C3d 的潜力，作为心肌 IRI 小鼠模型中心肌补体激活的标志物。我们将单光子发射计算机断层扫描 (SPECT) 与 99mTechnecium 标记的重组补体受体 2 (99mTc-rCR2) 结合使用，后者特异性检测补体激活位点的 C3d。与在 C3 缺陷小鼠中使用失活 CR2 突变体 (99mTc-K41E CR2) 或无关蛋白 (99mTc-PSMA) 或使用 99mTc-rCR2 进行对照成像相比，在补体完整小鼠中使用 99mTc-rCR2 在再灌注心肌中产生了特异性摄取。 99mTc-rCR2 的心脏与骨骼肌的比率显着高于三个对照组。组织学分析证实了 99mTc-rCR2 的特异性摄取。在治疗性抑制补体 C3 激活后，我们发现心肌对 99mTc-rCR2 的摄取减少。因此，我们得出结论，99mTc-rCR2 成像可用于非侵入性检测激活的补体，并且将来可用于量化补体激活引起的心肌损伤的严重程度。
Complement activation is a recognised mediator of myocardial ischaemia-reperfusion-injury (IRI) and cardiomyocytes are a known source of complement proteins including the central component C3, whose activation products can mediate tissue inflammation, cell death and profibrotic signalling. We investigated the potential to detect and quantify the stable covalently bound product C3d by external body imaging, as a marker of complement activation in heart muscle in a murine model of myocardial IRI. We used single-photon-emission-computed-tomography (SPECT) in conjunction with 99mTechnecium-labelled recombinant complement receptor 2 (99mTc-rCR2), which specifically detects C3d at the site of complement activation. Compared to control imaging with an inactive CR2 mutant (99mTc-K41E CR2) or an irrelevant protein (99mTc-PSMA) or using 99mTc-rCR2 in C3-deficient mice, the use of 99mTc-rCR2 in complement-intact mice gave specific uptake in the reperfused myocardium. The heart to skeletal muscle ratio of 99mTc-rCR2 was significantly higher than in the three control groups. Histological analysis confirmed specific uptake of 99mTc-rCR2. Following therapeutic inhibition of complement C3 activation, we found reduced myocardial uptake of 99mTc-rCR2. We conclude, therefore that 99mTc-rCR2 imaging can be used for non-invasive detection of activated complement and in future could be exploited to quantify the severity of myocardial damage due to complement activation.
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影响因子：
9.5
作者：
Pischke SE;Gustavsen A;Orrem HL;Egge KH;Courivaud F;Fontenelle H;Despont A;Bongoni AK;Rieben R;Tønnessen TI;Nunn MA;Scott H;Skulstad H;Barratt-Due A;Mollnes TE
通讯作者：
Mollnes TE
DOI：
10.1016/j.jtcvs.2010.08.035
发表时间：
2011-07-01
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作者：
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通讯作者：
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影响因子：
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作者：
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