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心血管损伤后全身中性粒细胞动态变化的无创性图谱绘制。

Non-invasive mapping of systemic neutrophil dynamics upon cardiovascular injury.

作者信息

Bouvain Pascal, Ding Zhaoping, Kadir Shiwa, Kleimann Patricia, Kluge Nils, Tiren Zeynep-Büsra, Steckel Bodo, Flocke Vera, Zalfen Ria, Petzsch Patrick, Wachtmeister Thorsten, John Gordon, Subramaniam Nirojah, Krämer Wolfgang, Strasdeit Tobias, Mehrabipour Mehrnaz, Moll Jens M, Schubert Rolf, Ahmadian Mohammad Reza, Bönner Florian, Boeken Udo, Westenfeld Ralf, Engel Daniel Robert, Kelm Malte, Schrader Jürgen, Köhrer Karl, Grandoch Maria, Temme Sebastian, Flögel Ulrich

机构信息

Experimental Cardiovascular Imaging, Institute for Molecular Cardiology, Heinrich Heine University, Düsseldorf, Germany.

Biological and Medical Research Center (BMFZ), Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.

出版信息

Nat Cardiovasc Res. 2023 Feb;2(2):126-143. doi: 10.1038/s44161-022-00210-w. Epub 2023 Feb 6.

DOI:10.1038/s44161-022-00210-w
PMID:39196054
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11357992/
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.

摘要

中性粒细胞在组织损伤的发生以及随后的消退和愈合过程中发挥着复杂的作用。为了评估心血管损伤时中性粒细胞的动态变化，我们在此开发了一种非侵入性、无背景干扰的方法，通过使用经工程改造的靶向多模态载氟纳米示踪剂进行全身磁共振成像，对中性粒细胞动态进行特异性成像，这些示踪剂带有专门针对小鼠或人类中性粒细胞的结合肽。在损伤前静脉注射示踪剂，可以对中性粒细胞在其不同造血微环境中的全身分布进行非侵入性三维可视化，并随后监测它们向受影响组织的迁移。由于其靶受体上调，受刺激的小鼠和人类中性粒细胞表现出增强的标记，这可作为体内无菌和非无菌心血管炎症中其激活状态的读出指标。这种非侵入性方法将使我们能够识别患者体内细菌或无菌性炎症的隐匿来源，并揭示由于中性粒细胞浸润或激活增强而处于严重恶化边缘的心血管疾病状态。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19d8/11357992/2f197a147ddf/44161_2022_210_Fig18_ESM.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19d8/11357992/2f197a147ddf/44161_2022_210_Fig18_ESM.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19d8/11357992/e62629f1de44/44161_2022_210_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19d8/11357992/9158a8efeb88/44161_2022_210_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19d8/11357992/21ff2382d2dc/44161_2022_210_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19d8/11357992/4984d67c401f/44161_2022_210_Fig9_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19d8/11357992/4c3e241c4b76/44161_2022_210_Fig10_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19d8/11357992/0078e4322b8c/44161_2022_210_Fig11_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19d8/11357992/44c20aa2d93c/44161_2022_210_Fig12_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19d8/11357992/5473b2894bf2/44161_2022_210_Fig13_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19d8/11357992/1bbdb7680ff7/44161_2022_210_Fig14_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19d8/11357992/b559e3e6bf5a/44161_2022_210_Fig15_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19d8/11357992/8149a8d19832/44161_2022_210_Fig16_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19d8/11357992/64f427bf1ae1/44161_2022_210_Fig17_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19d8/11357992/2f197a147ddf/44161_2022_210_Fig18_ESM.jpg

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