Center for Comparative Respiratory Biochemistry and Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, School of Medicine, University of California-Davis, 451 Health Sciences Drive, Davis, CA 95616, USA.
Toxicol Appl Pharmacol. 2011 Dec 1;257(2):182-8. doi: 10.1016/j.taap.2011.09.003. Epub 2011 Sep 16.
The mechanistic basis of the high toxicity to lung macrophages of coarse PM from the California wildfires of 2008 was examined in cell culture experiments with mouse macrophages. Wildfire PM directly killed macrophages very rapidly in cell culture at relatively low doses. The wildfire coarse PM is about four times more toxic to macrophages on an equal weight basis than the same sized PM collected from normal ambient air (no wildfires) from the same region and season. There was a good correlation between the extent of cytotoxicity and the amount of oxidative stress observed at a given dose of wildfire PM in vitro. Our data implicate NF-κB signaling in the response of macrophages to wildfire PM, and suggest that most, if not all, of the cytotoxicity of wildfire PM to lung macrophages is the result of oxidative stress. The relative ratio of toxicity and of expression of biomarkers of oxidant stress between wildfire PM and "normal" PM collected from ambient air is consistent with our previous results in mice in vivo, also suggesting that most, if not all, of the cytotoxicity of wildfire PM to lung macrophages is the result of oxidative stress. Our findings from this and earlier studies suggest that the active components of coarse PM from the wildfire are heat-labile organic compounds. While we cannot rule out a minor role for endotoxin in coarse PM preparations from the collected wildfire PM in our observed results both in vitro and in vivo, based on experiments using the inhibitor Polymyxin B most of the oxidant stress and pro-inflammatory activity observed was not due to endotoxin.
我们以细胞培养实验的方式研究了 2008 年加利福尼亚野火产生的粗颗粒物对肺巨噬细胞产生高毒性的机制。在细胞培养中，野火 PM 以相对较低的剂量直接迅速杀死巨噬细胞。基于同等重量，与同一地区和季节正常环境空气中采集的相同大小的 PM 相比，来自野火的粗颗粒物对巨噬细胞的毒性约高四倍。在体外，观察到一定剂量的野火 PM 产生的细胞毒性与氧化应激程度之间存在良好的相关性。我们的数据表明 NF-κB 信号通路参与了巨噬细胞对野火 PM 的反应，并表明野火 PM 对肺巨噬细胞的大部分（如果不是全部）细胞毒性是氧化应激的结果。与从环境空气中采集的“正常”PM 相比，野火 PM 的毒性和氧化应激生物标志物表达的相对比值与我们之前在体内进行的小鼠研究结果一致，这也表明野火 PM 对肺巨噬细胞的大部分细胞毒性是氧化应激的结果。我们从这项研究和之前的研究中发现，野火粗颗粒物中的活性成分是热不稳定的有机化合物。虽然我们不能排除收集的野火 PM 粗颗粒物制剂中的内毒素在我们的体外和体内观察结果中起次要作用，但基于使用抑制剂 Polymyxin B 的实验，观察到的大部分氧化应激和促炎活性不是由于内毒素引起的。
