Activated neutrophil fluorescent imaging technique for human lungs.

Activated neutrophil fluorescent imaging technique for human lungs.
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人肺激活的中性粒细胞荧光成像技术。

DOI:
10.1038/s41598-020-80083-w
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发表时间:
2021-01-13
期刊:
影响因子:
4.6
通讯作者:
Dhaliwal K
Dhaliwal K
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Craven TH;Walton T;Akram AR;Scholefield E;McDonald N;Marshall ADL;Humphries DC;Mills B;Campbell TA;Bruce A;Mair J;Dear JW;Newby DE;Hill AT;Walsh TS;Haslett C;Dhaliwal K

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神经元活化是急性炎症的一个组成过程,并与不良临床后遗症相关。在患者肺部真实的时间内鉴定嗜中性粒细胞活化可以允许在通常由临床标准定义的其他异质性群组中对患者进行生物分层。目前不存在用于在患者的肺中真实的时间内鉴定嗜中性粒细胞活化的方法。我们开发了一种定制的分子成像探针,靶向中性粒细胞激活的三个特征:胞饮作用,吞噬体碱化和人中性粒细胞弹性蛋白酶(HNE)活性。探针在体外和离体条件下均按设计发挥功能。我们在健康志愿者、支气管扩张患者和严重机械通气不良患者的床边使用探针实时评价了中性粒细胞活性的光学显微内镜成像。我们在体内检测到一系列成像反应,反映了病情和严重程度的异质性。我们证实光信号是由于探针功能和中性粒细胞活化。
Neutrophil activation is an integral process to acute inflammation and is associated with adverse clinical sequelae. Identification of neutrophil activation in real time in the lungs of patients may permit biological stratification of patients in otherwise heterogenous cohorts typically defined by clinical criteria. No methods for identifying neutrophil activation in real time in the lungs of patients currently exist. We developed a bespoke molecular imaging probe targeting three characteristic signatures of neutrophil activation: pinocytosis, phagosomal alkalinisation, and human neutrophil elastase (HNE) activity. The probe functioned as designed in vitro and ex vivo. We evaluated optical endomicroscopy imaging of neutrophil activity using the probe in real-time at the bedside of healthy volunteers, patients with bronchiectasis, and critically unwell mechanically ventilated patients. We detected a range of imaging responses in vivo reflecting heterogeneity of condition and severity. We corroborated optical signal was due to probe function and neutrophil activation.
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