Wilson Martin R, Lightbody Janet H, Donaldson Ken, Sales Jill, Stone Vicki
Biomedicine Research Group, School of Life Sciences, Napier University, 10 Colinton Road, Edinburgh, EH10 5DT, Scotland.
Toxicol Appl Pharmacol. 2002 Nov 1;184(3):172-9. doi: 10.1006/taap.2002.9501.
Both the ultrafine particle and transition metal components of particulate air pollution (PM(10)) have been hypothesized to be important factors in determining toxicity and potential adverse health effects. In this study we aimed to investigate interactions between transition metal salts and a surrogate environmental particle-ultrafine carbon black (ufCB). In all experimental systems employed, the ufCB was found to be more reactive than its fine counterpart (CB). Incubation of ufCB with the reactive oxygen species (ROS)-sensitive probe dichlorofluorescin in the absence of cells generated significantly more ROS than CB. With addition of either cupric sulfate (CuSO(4)), ferrous sulfate (FeSO(4)), or ferric chloride (FeCl(3)), the ROS generation in the presence of ufCB was enhanced in a potentiative manner. In Mono Mac 6 macrophages, ufCB again produced more ROS than CB. However, addition of iron salts had no additive effect over and above that induced in the macrophages by ufCB. In the mouse macrophage cell line J774, ufCB decreased the cellular content of GSH and ATP. Addition of iron further decreased both GSH and ATP and a potentiative interaction between ufCB and FeSO(4) was observed, but only at the highest iron concentrations tested. A concentration-dependent increase in tumor necrosis factor-alpha production by J774 cells was also observed following exposure to ufCB, which was not further enhanced by the addition of iron. J774 cells were also found to sequester or chelate iron without inducing toxicity. In the rat lung ufCB induced a significant neutrophil influx and this inflammatory effect was potentiativelly enhanced by the addition of FeCl(3) (100 microM). These findings suggest that (1) ultrafine particles and metals interact by chemical potentiation in a cell-free environment to generate ROS, (2) potentiation between ultrafine particles and metal salts is not observed in the presence of macrophages as iron is sequestered or chelated by the cells, (3) in the lung, ultrafine particles and iron salts interact in a potentiative manner to generate inflammation.
空气污染颗粒物（PM(10)）中的超细颗粒成分和过渡金属成分均被假定为决定毒性和潜在健康不良影响的重要因素。在本研究中，我们旨在探究过渡金属盐与一种替代环境颗粒——超细炭黑（ufCB）之间的相互作用。在所有采用的实验系统中，发现ufCB比其细颗粒对应物（CB）更具反应活性。在无细胞情况下，将ufCB与活性氧（ROS）敏感探针二氯荧光素一起孵育产生的ROS显著多于CB。添加硫酸铜（CuSO(4)）、硫酸亚铁（FeSO(4)）或氯化铁（FeCl(3)）后，在ufCB存在时ROS的产生以增效方式增强。在单核巨噬细胞6（Mono Mac 6）巨噬细胞中，ufCB产生的ROS再次多于CB。然而，添加铁盐在ufCB诱导巨噬细胞产生的ROS基础上没有额外的相加效应。在小鼠巨噬细胞系J774中，ufCB降低了谷胱甘肽（GSH）和三磷酸腺苷（ATP）的细胞含量。添加铁进一步降低了GSH和ATP，并且观察到ufCB与FeSO(4)之间存在增效相互作用，但仅在测试的最高铁浓度下。暴露于ufCB后，J774细胞产生的肿瘤坏死因子-α也呈浓度依赖性增加，添加铁并未进一步增强这种增加。还发现J774细胞能螯合或结合铁而不诱导毒性。在大鼠肺中，ufCB诱导了显著的中性粒细胞流入，添加FeCl(3)（100 microM）后这种炎症效应以增效方式增强。这些发现表明：（1）在无细胞环境中，超细颗粒和金属通过化学增效相互作用产生ROS；（2）在巨噬细胞存在时未观察到超细颗粒与金属盐之间的增效作用，因为铁被细胞螯合或结合；（3）在肺中，超细颗粒和铁盐以增效方式相互作用产生炎症。
