Proteomic analysis of bronchoalveolar lavage fluid: effect of acute exposure to diesel exhaust particles in rats.

Proteomic analysis of bronchoalveolar lavage fluid: effect of acute exposure to diesel exhaust particles in rats.
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DOI:
10.1289/ehp.9745
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发表时间:
2007-05
影响因子:
10.4
通讯作者:
Knechtges PL
Knechtges PL
中科院分区:
环境科学与生态学1区
文献类型:
--
作者:
Lewis JA;Rao KM;Castranova V;Vallyathan V;Dennis WE;Knechtges PL

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柴油机尾气颗粒物(DEPs)的吸入以肺损伤和炎症为特征,多形核白细胞和肺泡巨噬细胞的数量显著增加。这种细胞浸润的流入与多种基因的激活有关,包括细胞因子和趋化因子,以及活性氧的产生。肺损伤的发病机制尚未完全了解,但已观察到肺中许多蛋白质的存在或丰度的改变。我们在这项研究中的目的是进一步描述这些变化,并询问是否可以使用现代蛋白质组学技术识别其他变化。本研究调查了大鼠暴露于5,35或50 mg/kg动物体重的DEP后1,7或30天的支气管肺泡灌洗液蛋白质组的总体变化。通过表面增强激光解吸/电离-飞行时间质谱法进行的分析确定了两个不同的峰,这两个峰在所有动物的所有剂量下均表现为急性反应。我们通过使用液相色谱-质谱联用的额外质谱研究,将这两个峰(质荷比(m/z)为9,100和10,100)鉴定为过敏毒素C3 a和钙颗粒蛋白A。通过这种方法,我们发现了一些炎症反应蛋白,这些蛋白可能与DEP暴露引起的炎症早期阶段有关。进一步的研究是必要的,以确定这些蛋白质的血清水平是否可以柴油废气暴露工人的标志物。
Inhalation of diesel exhaust particles (DEPs) is characterized by lung injury and inflammation, with significant increases in the numbers of polymorphonuclear leukocytes and alveolar macrophages. This influx of cellular infiltrates is associated with the activation of multiple genes, including cytokines and chemokines, and the production of reactive oxygen species. The pathogenesis of the lung injury is not fully understood, but alterations in the presence or abundance of a number of proteins in the lung have been observed. Our objective in this study was to further characterize these changes and to ask whether additional changes could be discerned using modern proteomic techniques. The present study investigates global alterations in the proteome of bronchoalveolar lavage fluid taken from rats 1, 7, or 30 days after exposure to 5, 35, or 50 mg/kg of animal weight of DEPs. Analysis by surface-enhanced laser desorption/ionization–time of flight mass spectrometry identified two distinct peaks that appeared as an acute response postexposure at all doses in all animals. We identified these two peaks, with mass to charge ratios (m/z) of 9,100 and 10,100, as anaphylatoxin C3a and calgranulin A by additional mass spectral investigation using liquid chromatography coupled to mass spectrometry. With this approach, we found a number of inflammatory response proteins that may be associated with the early phases of inflammation in response to DEP exposure. Further studies are warranted to determine whether serum levels of these proteins could be markers of diesel exhaust exposure in workers.
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