Monoclonal antibody 2C5 specifically targets neutrophil extracellular traps.

Monoclonal antibody 2C5 specifically targets neutrophil extracellular traps.
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DOI:
10.1080/19420862.2020.1850394
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发表时间:
2020-01
期刊:
影响因子:
5.3
通讯作者:
Torchilin VP
Torchilin VP
中科院分区:
医学2区
文献类型:
--
作者:
Mendes LP;Rostamizadeh K;Gollomp K;Myerson JW;Marcos-Contreras OA;Zamora M;Luther E;Brenner JS;Filipczak N;Li X;Torchilin VP

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中性粒细胞可以释放DNA和颗粒状细胞质蛋白,形成堆叠核小体(NS)的光滑细丝。这些结构被称为中性粒细胞胞外陷阱(NETs),参与多种病理过程,NET的形成和去除在临床上具有重要意义。单克隆抗体2C5对完整的NS有很强的特异性,但对单个NS成分没有特异性,表明2C5可能潜在地靶向NETs中的NS。本研究利用中性粒细胞体外生成NETs,并将HL-60细胞分化为粒细胞样细胞。ELISA法测定了2C5对NETs的特异性,结果表明其与纯化核组蛋白底物的特异性相似。免疫荧光显示,在静态和灌注的微流体细胞培养中,即使在NET压实后,2C5也能染色NET。用2C5修饰脂质体可显著增强脂质体与NETs的关联。我们的研究结果表明,2C5可用于识别和可视化net,并可作为net靶向诊断和治疗的配体。
Neutrophils can release DNA and granular cytoplasmic proteins that form smooth filaments of stacked nucleosomes (NS). These structures, called neutrophil extracellular traps (NETs), are involved in multiple pathological processes, and NET formation and removal are clinically significant. The monoclonal antibody 2C5 has strong specificity toward intact NS but not to individual NS components, indicating that 2C5 could potentially target NS in NETs. In this study, NETs were generated in vitro using neutrophils and HL-60 cells differentiated into granulocyte-like cells. The specificity of 2C5 toward NETs was evaluated by ELISA, which showed that it binds to NETs with the specificity similar to that for purified nucleohistone substrate. Immunofluorescence showed that 2C5 stains NETs in both static and perfused microfluidic cell cultures, even after NET compaction. Modification of liposomes with 2C5 dramatically enhanced liposome association with NETs. Our results suggest that 2C5 could be used to identify and visualize NETs and serve as a ligand for NET-targeted diagnostics and therapies.
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