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用于评估时间蛋白质组学的成像质谱:鲍曼不动杆菌肺部感染中钙卫蛋白的分析

Imaging mass spectrometry for assessing temporal proteomics: analysis of calprotectin in Acinetobacter baumannii pulmonary infection.

作者信息

Moore Jessica L, Becker Kyle W, Nicklay Joshua J, Boyd Kelli L, Skaar Eric P, Caprioli Richard M

机构信息

Department of Chemistry, Vanderbilt University, Nashville, TN, USA.

Mass Spectrometry Research Center, Vanderbilt University, School of Medicine, Nashville, TN, USA.

出版信息

Proteomics. 2014 Apr;14(7-8):820-828. doi: 10.1002/pmic.201300046. Epub 2013 Jul 24.

Abstract

Imaging MS is routinely used to show spatial localization of proteins within a tissue sample and can also be employed to study temporal protein dynamics. The antimicrobial S100 protein calprotectin, a heterodimer of subunits S100A8 and S100A9, is an abundant cytosolic component of neutrophils. Using imaging MS, calprotectin can be detected as a marker of the inflammatory response to bacterial challenge. In a murine model of Acinetobacter baumannii pneumonia, protein images of S100A8 and S100A9 collected at different time points throughout infection aid in visualization of the innate immune response to this pathogen. Calprotectin is detectable within 6 h of infection as immune cells respond to the invading pathogen. As the bacterial burden decreases, signals from the inflammatory proteins decrease. Calprotectin is no longer detectable 96-144 h post infection, correlating to a lack of detectable bacterial burden in lungs. These experiments provide a label-free, multiplexed approach to study host response to a bacterial threat and eventual clearance of the pathogen over time.

摘要

成像质谱法通常用于显示组织样本中蛋白质的空间定位,也可用于研究蛋白质的动态变化。抗菌性S100蛋白钙卫蛋白是亚基S100A8和S100A9的异二聚体,是中性粒细胞中丰富的胞质成分。使用成像质谱法,钙卫蛋白可作为细菌攻击炎症反应的标志物被检测到。在鲍曼不动杆菌肺炎的小鼠模型中,在感染全过程的不同时间点收集的S100A8和S100A9的蛋白质图像有助于可视化对该病原体的固有免疫反应。感染后6小时内,随着免疫细胞对入侵病原体作出反应,可检测到钙卫蛋白。随着细菌载量的减少,炎症蛋白的信号也会减弱。感染后96 - 144小时,钙卫蛋白不再可检测到,这与肺部缺乏可检测到的细菌载量相关。这些实验提供了一种无需标记的多重方法,用于研究宿主对细菌威胁的反应以及病原体随时间的最终清除情况。

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