Interactions between ultrafine particles and transition metals in vivo and in vitro.
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.
Wilson
Martin R
MR
Biomedicine Research Group, School of Life Sciences, Napier University, 10 Colinton Road, Edinburgh, EH10 5DT, Scotland.
Lightbody
Janet H
JH
Donaldson
Ken
K
Sales
Jill
J
Stone
Vicki
V
D000255:Adenosine Triphosphate / Q000378:metabolism; D000393:Air Pollutants; D000818:Animals; D002244:Carbon / Q000008:administration & dosage / Q000633:toxicity*; D002460:Cell Line; D003300:Copper / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007442:Intubation, Intratracheal; D007501:Iron / Q000378:metabolism / Q000633:toxicity*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000393:Air Pollutants; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D002244:Carbon; D003300:Copper; D000255:Adenosine Triphosphate; D007501:Iron; D005978:Glutathione