The potential health effects of transition metals in particulate air pollution

Background: Inhaled air contains myriad potential toxicants, which vary by source and site. These may include particulate matter (PM) containing transition metals, polyaromatic hydrocarbons and soot, aeroallergens, and pathogens. Different toxicants exert their deleterious effects via a variety of mechanisms, and may also differentially affect individuals depending on other factors such as the presence of disease.Methods: Size-fractionated airborne particulate matter (10-2.5 µm, <2.5 µm, <0.18 µm) was collected at a busy mainline underground railway station. PM composition was analysed by inductively-coupled plasma mass spectrometry alongside comparator PM samples from a woodstove, roadwear simulator, and road tunnel. Underground railway PM-mediated generation of reactive oxygen species (ROS) was measured using dichlorofluorescein. Primary bronchial epithelial cells (PBECs) were cultured as monolayers and differentiated air-liquid interface (ALI) cultures before exposure to underground railway PM for 24 h. IL-8 release, barrier integrity, and antioxidant gene expression were assayed. Intracellular PM was studied by transmission EM. As a separate PM type, the effects of the allergenic fungus Alternaria alternata on PBECs were similarly examined, and interactions with underground railway PM were studied.Results: Underground PM was metal-rich, especially iron, and generated ROS in a concentration-, size-, and iron-dependent manner. PBEC monolayer cultures showed a moderate PM concentration-dependent increase in IL-8 release without LDH release, but this was absent in ALI cultures. There was observable intracellular PM 24 h post-challenge in ALI cultures, and an upregulation of antioxidant genes (HO-1, NQO1) which could be diminished by DFX and NAC. Alternaria extract induced a significant and marked concentration-dependent increase in IL-8 release and a drop in transepithelial electrical resistance (TER), predominantly due to a heat-labile serine protease. Alternaria extract appeared to have more pronounced effects on cells pre-treated with underground railway PM, but this was independent of a heat-labile component.Conclusion: Metal-rich underground railway PM potently generates ROS, with modest pro-inflammatory effects and a marked induction of antioxidant defences. The potential effects of PM entry into cells merits further study. The novel metal-rich nature of such an environmental ultrafine PM warrants further work in light of its high surface area/volume ratio and potential ability to penetrate into the alveoli and possibly the systemic circulation Additionally, the ability of underground railway PM to generate ROS potently suggests that individuals with defective antioxidant defences, such as seen in asthmatic airways, may be at heightened risk of the effects of metal-rich PM, as may those concomitantly exposed to airborne fungi