Lewis John A, Rao K Murali Krishna, Castranova Vince, Vallyathan Val, Dennis William E, Knechtges Paul L
US Army Center for Environmental Health Research, Fort Detrick, Maryland 21740, USA.
Environ Health Perspect. 2007 May;115(5):756-63. doi: 10.1289/ehp.9745. Epub 2007 Feb 5.
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.
吸入柴油废气颗粒（DEP）的特征是肺损伤和炎症，多形核白细胞和肺泡巨噬细胞数量显著增加。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，但已观察到肺中多种蛋白质的存在或丰度发生了改变。我们在本研究中的目的是进一步表征这些变化，并询问使用现代蛋白质组学技术是否能识别出其他变化。
本研究调查了暴露于5、35或50mg/kg动物体重的DEP后1、7或30天从大鼠获取的支气管肺泡灌洗液蛋白质组的整体变化。
通过表面增强激光解吸/电离飞行时间质谱分析，在所有动物的所有剂量下，暴露后均出现两个不同的峰，表现为急性反应。通过使用液相色谱-质谱联用的额外质谱研究，我们将这两个质荷比（m/z）分别为9100和10100的峰鉴定为过敏毒素C3a和钙粒蛋白A。
通过这种方法，我们发现了一些可能与DEP暴露引起的炎症早期阶段相关的炎症反应蛋白。有必要进一步研究以确定这些蛋白质的血清水平是否可作为工人接触柴油废气的标志物。
