Non-invasive mapping of systemic neutrophil dynamics upon cardiovascular injury

心血管损伤时全身中性粒细胞动力学的无创映射

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作者:Pascal Bouvain, Zhaoping Ding, Shiwa Kadir, Patricia Kleimann, Nils Kluge, Zeynep-Büsra Tiren, Bodo Steckel, Vera Flocke, Ria Zalfen, Patrick Petzsch, Thorsten Wachtmeister, Gordon John, Nirojah Subramaniam, Wolfgang Krämer, Tobias Strasdeit, Mehrnaz Mehrabipour, Jens M Moll, Rolf Schubert, Mohammad

Abstract

Neutrophils play a complex role during onset of tissue injury and subsequent resolution and healing. To assess neutrophil dynamics upon cardiovascular injury, here we develop a non-invasive, background-free approach for specific mapping of neutrophil dynamics by whole-body magnetic resonance imaging using targeted multimodal fluorine-loaded nanotracers engineered with binding peptides specifically directed against murine or human neutrophils. Intravenous tracer application before injury allowed non-invasive three-dimensional visualization of neutrophils within their different hematopoietic niches over the entire body and subsequent monitoring of their egress into affected tissues. Stimulated murine and human neutrophils exhibited enhanced labeling due to upregulation of their target receptors, which could be exploited as an in vivo readout for their activation state in both sterile and nonsterile cardiovascular inflammation. This non-invasive approach will allow us to identify hidden origins of bacterial or sterile inflammation in patients and also to unravel cardiovascular disease states on the verge of severe aggravation due to enhanced neutrophil infiltration or activation.

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