Non-Invasive whole-body detection of complement activation using radionuclide imaging in a mouse model of myocardial ischaemia-reperfusion injury

Autor: Sharif-Paghaleh, Ehsan, Yap, May Lin, Puhl, Sarah-Lena, Badar, Adam, Torres, Julia Baguña, Chuamsaamarkkee, Krisanat, Kampmeier, Florian, Smith, Richard A., Clark, James, Blower, Philip J., Sacks, Steven, Mullen, Gregory E.
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: Scientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
Sharif-Paghaleh, E, Clark, J, Yap, M L, Badar, A, Baguna Torres, J, Puhl, S L, Blower, P J, Chuamsaamarkkee, K, Kampmeier, F, Smith, R, Sacks, S H & Mullen, G E D 2017, ' Non-Invasive whole-body detection of complement activation using radionuclide imaging in a mouse model of myocardial ischaemia-reperfusion injury ', Scientific Reports, vol. 7, no. 1, 16090 . https://doi.org/10.1038/s41598-017-16387-1
Scientific Reports
ISSN: 2045-2322
DOI: 10.1038/s41598-017-16387-1
Popis: 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.
Databáze: OpenAIRE
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