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蜱唾液蛋白 Evasin-3 通过与激活的内皮细胞上沉积的 CXC 型趋化因子相互作用,可实现动脉炎症的可视化。

Tick Saliva Protein Evasin-3 Allows for Visualization of Inflammation in Arteries through Interactions with CXC-Type Chemokines Deposited on Activated Endothelium.

机构信息

Institute for Cardiovascular Prevention, Ludwig-Maximilians-University, Pettenkoferstraße 8a, 80336, Munich, Germany.

出版信息

Bioconjug Chem. 2020 Mar 18;31(3):948-955. doi: 10.1021/acs.bioconjchem.0c00095. Epub 2020 Mar 4.

DOI:10.1021/acs.bioconjchem.0c00095
PMID:32077689
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7086393/
Abstract

Atherosclerosis is one of the leading causes of mortality in developed and developing countries. The onset of atherosclerosis development is accompanied by overexpression of several inflammatory chemokines. Neutralization of these chemokines by chemokine-binding agents attenuates atherosclerosis progression. Here, we studied structural binding features of the tick protein Evasin-3 to chemokine (C-X-C motif) ligand (CXCL1). We showed that Evasin-3-bound CXCL1 is unable to activate the CXCR2 receptor, but retains affinity to glycosaminoglycans. This observation was exploited to detect inflammation by visualizing a group of closely related CXC-type chemokines deposited on cell walls in human endothelial cells and murine carotid arteries by a fluorescent Evasin-3 conjugate. This work highlights the applicability of tick-derived chemokine-binding conjugates as a platform for the development of new agents for inflammation imaging.

摘要

动脉粥样硬化是发达国家和发展中国家主要的死亡原因之一。动脉粥样硬化发展的发生伴随着几种炎症趋化因子的过度表达。趋化因子结合剂中和这些趋化因子可减轻动脉粥样硬化的进展。在这里,我们研究了蜱蛋白 Evasin-3 与趋化因子(C-X-C 基序)配体(CXCL1)的结构结合特征。我们表明,Evasin-3 结合的 CXCL1 无法激活 CXCR2 受体,但保留与糖胺聚糖的亲和力。这一观察结果被利用来通过荧光 Evasin-3 缀合物可视化在人内皮细胞和鼠颈动脉壁上沉积的一组密切相关的 CXC 型趋化因子,从而检测炎症。这项工作强调了蜱衍生趋化因子结合物作为开发新的炎症成像剂的平台的适用性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa40/7086393/8c4219ee3cce/bc0c00095_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa40/7086393/bf549e481ed4/bc0c00095_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa40/7086393/2997a51886ad/bc0c00095_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa40/7086393/695e02a2362c/bc0c00095_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa40/7086393/704f88b517f6/bc0c00095_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa40/7086393/d86c7eebedab/bc0c00095_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa40/7086393/8c4219ee3cce/bc0c00095_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa40/7086393/bf549e481ed4/bc0c00095_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa40/7086393/2997a51886ad/bc0c00095_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa40/7086393/695e02a2362c/bc0c00095_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa40/7086393/704f88b517f6/bc0c00095_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa40/7086393/d86c7eebedab/bc0c00095_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa40/7086393/8c4219ee3cce/bc0c00095_0006.jpg

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Int J Mol Sci. 2022 Apr 11;23(8):4205. doi: 10.3390/ijms23084205.
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