Madden Michael C, Dailey Lisa A, Stonehuerner Jacqueline G, Harris Bruce D
National Health and Environmmental Effects Research Laboratory, ORD, U.S. EPA, Research Triangle Park, NC, USA.
J Toxicol Environ Health A. 2003 Dec 26;66(24):2281-97. doi: 10.1080/15287390390244292.
Epidemiologic evidence suggests that increased morbidity and mortality are associated with the concentrations of ambient air particulate matter (PM). Many sources contribute to the particulate fraction of ambient air pollution, including diesel exhaust particulates (DEP). Diesel exhaust also contributes gas-phase pollutants to the atmosphere, and gaseous copollutants may influence the toxicity of PM. The composition of diesel exhaust varies greatly depending on the engine load conditions as well as other factors. To determine whether different diesel exhaust composition can affect lung cell resposes, the effects of of diesel exhaust extracts derived from different engine loads were examined on normal human bronchial epithelial cells (NHBE) in vitro. Diesel exhaust was collected into chilled impingers containing phosphate-buffered saline (PBS). Cultured NHBE cells were treated with 0 to 500 microg/well extract from approximately 0% engine load (termed low load or LL) or extract from approximately 75% engine load (termed high load or HL) for 24 h. The HL extract was cytotoxic at 500 microg compared to controls as measured by (51)Cr release. Production of the neutrophil chemotaxin interleukin 8 (IL-8) was decreased 4.7-fold in cells treated with 500 microg LL extract, whereas cells treated with 500 microg HL extract showed a 2.4-fold increase in IL-8 release. Production of the inflammatory and immune system mediator prostaglandin E(2) (PGE(2)) was increased up to 2.5-fold in cells treated with HL extract, but unchanged with other treatments. Melittin stimulation of cells showed that the LL extract had an inhibitory effect on PGE(2) release at 500 microg. Differences in carbonyl content of the extracts were found by high performance liquid chromatography/mass spectroscopy HPLC/MS, with the HL extract having more intermediate size carbonyls (i.e. with six to nine carbons). The data suggest that the response of NHBE cells to treatment with diesel exhaust will vary depending on the constituent components of the exhaust.
流行病学证据表明，发病率和死亡率的增加与环境空气中颗粒物（PM）的浓度有关。许多来源导致了环境空气污染中的颗粒物部分，包括柴油废气颗粒物（DEP）。柴油废气还会向大气中排放气相污染物，气态共污染物可能会影响PM的毒性。柴油废气的成分会因发动机负载条件以及其他因素而有很大差异。为了确定不同的柴油废气成分是否会影响肺细胞反应，研究了源自不同发动机负载的柴油废气提取物对正常人支气管上皮细胞（NHBE）的体外影响。将柴油废气收集到含有磷酸盐缓冲盐水（PBS）的冷却冲击器中。用来自约0%发动机负载的0至500微克/孔提取物（称为低负载或LL）或来自约75%发动机负载的提取物（称为高负载或HL）处理培养的NHBE细胞24小时。通过（51）Cr释放测量，与对照相比，500微克的HL提取物具有细胞毒性。在用500微克LL提取物处理的细胞中，中性粒细胞趋化因子白细胞介素8（IL-8）的产生减少了4.7倍，而用500微克HL提取物处理的细胞中IL-8释放增加了2.4倍。在用HL提取物处理的细胞中，炎症和免疫系统介质前列腺素E2（PGE2）的产生增加了高达2.5倍，但其他处理则无变化。蜂毒肽刺激细胞表明，500微克的LL提取物对PGE2释放具有抑制作用。通过高效液相色谱/质谱联用（HPLC/MS）发现提取物的羰基含量存在差异，HL提取物具有更多中等大小的羰基（即含有6至9个碳）。数据表明，NHBE细胞对柴油废气处理的反应将因废气的组成成分而异。
