Monn C, Becker S
Federal Institute of Technology, Institute for Hygiene and Applied Physiology, Zurich, 8092, Switzerland.
Toxicol Appl Pharmacol. 1999 Mar 15;155(3):245-52. doi: 10.1006/taap.1998.8591.
Increased incidence of mortality and morbidity due to cardiopulmonary complications has been found to associate with elevated levels of particulate air pollution (particulate matter with an aerodynamic diameter < 10 microm, PM10 and <2.5 microm, PM2. 5). Lung injury and an imbalance of inflammatory mediators are proposed causative mechanisms, while the toxic constituents may be acidity, transition metals, organic, and biogenic materials. To compare the ability of inhalable fine particles (PM2.5), and coarse particles (PM10-2.5) to cause cell injury and cytokine production in monocytes, dichotomous Andersen samplers were used to collect size-fractionated PM10 for in vitro testing of the particle extracts. Particles from both outdoor and indoor air were collected onto Teflon filters, on nine separate occasions. Each filter was water extracted and each extract assessed for ability to cause cell death, as well as interleukin (IL)-6 and IL-8 production in human monocytes. Significant toxicity and cytokine production was induced by outdoor PM10-2.5, but not by outdoor PM2.5 or the particles collected indoors. Outdoor PM10-2.5 induced 20 times the amounts of IL-6 and IL-8 than the fine particles. Cytotoxicity was inhibited by deferoxamine, a chelator of transition metals, while cytokine production was not. On the other hand, lipopolysaccharide binding protein (LBP) completely inhibited cytokine induction by PM10-2.5, suggesting that gram-negative bacteria and/or endotoxins are components of PM10-2.5. The effective proinflammatory effects of endotoxin on macrophages may upset lung homeostasis while metals-induced cytotoxicity/necrosis may set up inflammation independent of macrophage-derived cytokines.
已发现,心肺并发症导致的死亡率和发病率增加与空气中细颗粒物污染水平升高(空气动力学直径<10微米的颗粒物,即PM10和<2.5微米的颗粒物,即PM2.5)有关。肺损伤和炎症介质失衡被认为是致病机制,而有毒成分可能是酸度、过渡金属、有机物和生物源物质。为了比较可吸入细颗粒物(PM2.5)和粗颗粒物(PM10 - 2.5)在单核细胞中引起细胞损伤和细胞因子产生的能力,使用二分法安德森采样器收集分级粒径的PM10,用于颗粒提取物的体外测试。在九个不同场合,将室外和室内空气中的颗粒物收集到聚四氟乙烯滤膜上。每个滤膜进行水提取,然后评估每种提取物导致细胞死亡的能力,以及在人单核细胞中产生白细胞介素(IL)-6和IL -8的能力。室外PM10 - 2.5可诱导显著的毒性和细胞因子产生,但室外PM2.5或室内收集的颗粒物则不会。室外PM10 - 2.5诱导产生的IL -6和IL -8量是细颗粒物的20倍。过渡金属螯合剂去铁胺可抑制细胞毒性,但不能抑制细胞因子产生。另一方面,脂多糖结合蛋白(LBP)可完全抑制PM10 - 2.5诱导的细胞因子产生,这表明革兰氏阴性菌和/或内毒素是PM10 - 2.5的组成成分。内毒素对巨噬细胞的有效促炎作用可能会破坏肺内稳态,而金属诱导的细胞毒性/坏死可能会引发独立于巨噬细胞衍生细胞因子的炎症。