Ultrafine particulate pollutants induce oxidative stress and mitochondrial damage.

Abstract

The objectives of this study were to determine whether differences in the size and composition of coarse (2.5-10 µm), fine (< 2.5 µm), and ultrafine (< 0.1 µm) particulate matter (PM) are related to their uptake in macrophages and epithelial cells and their ability to induce oxidative stress. The premise for this study is the increasing awareness that various PM components induce pulmonary inflammation through the generation of oxidative stress. Coarse, fine, and ultrafine particles (UFPs) were collected by ambient particle concentrators in the Los Angeles basin in California and used to study their chemical composition in parallel with assays for generation of reactive oxygen species (ROS) and ability to induce oxidative stress in macrophages and epithelial cells. UFPs were most potent toward inducing cellular heme oxygenase-1 (HO-1) expression and depleting intracellular glutathione. HO-1 expression, a sensitive marker for oxidative stress, is directly correlated with the high organic carbon and polycyclic aromatic hydrocarbon (PAH) content of UFPs. The dithiothreitol (DTT) assay, a quantitative measure of in vitro ROS formation, was correlated with PAH content and HO-1 expression. UFPs also had the highest ROS activity in the DTT assay. Because the small size of UFPs allows better tissue penetration, we used electron microscopy to study subcellular localization. UFPs and, to a lesser extent, fine particles, localize in mitochondria, where they induce major structural damage. This may contribute to oxidative stress. Our studies demonstrate that the increased biological potency of UFPs is related to the content of redox cycling organic chemicals and their ability to damage mitochondria.

Repeated hospital encounters for asthma in children and exposure to traffic-related air pollution near the home

“…25 Only 3 patients had 11 to 12 readmissions, so we considered only 10 or fewer readmissions per patient in the analysis. Patients were considered to be at risk for recurrence from the time of first hospital encounter until the end of the observation period (December 31,2003) or their 19th birthday. Time at risk started at the first or a subsequent event and ended with each season (when time at risk begins with the next seasonal exposure) or at the next event (when time at risk begins again with the current seasonal exposure).…”

“…Ultrafine particles carry more redox-active components than larger particles, which are more spatially homogenous. 7,31,32 Based in large part on experimental evidence, it has been hypothesized that particles from vehicular exhaust, especially in the ultrafine range, can trigger oxidative stress. When antioxidant responses are then overwhelmed, airway inflammation may follow, leading to increasing asthma symptoms in susceptible children.…”

Oxidative stress and anti-oxidative defense in schoolchildren residing in a petrochemical industry environment

“…The systemic inflammatory response to particulate air pollution and its relationship to adverse coronary events in (4,6,25). Polycyclic aromatic hydrocarbons (PAH) can induce OS indirectly through its biotransformation by liver enzymes to generate redox active quinones which act as catalysts for free radical production (5,6).…”

“…Polycyclic aromatic hydrocarbons (PAH) can induce OS indirectly through its biotransformation by liver enzymes to generate redox active quinones which act as catalysts for free radical production (5,6). In vitro reactive oxygen species (ROS) formation has been shown to be highly correlated with PAH content in air (6). The oxidation of membrane lipids, one of the primary events during oxidative cellular damage, can be assessed by measuring plasma MDA concentrations, a late-stage OS biomarker of injured cells and subcellular structures (26,27).…”

Seasonal and spatial trends in particle number concentrations and size distributions at the children's health study sites in Southern California

“…To this date, however, there appears to be heterogeneity in particulate matter (PM) concentrations and PMassociated health effects between locations within an urban setting, which raises considerable uncertainties as to whether PM mass, number, size, bulk or surface chemistry are the appropriate metrics associated with PM toxicity. For example, recent studies have shown that atmospheric ultrafine particles (with physical diameter o100 nm) have the potential for eliciting adverse health effect (Oberdo¨rster and Utell, 2002;Li et al, 2003Li et al, , 2004Xia et al, 2004). Recent epidemiological studies by Peters et al (1997) have demonstrated a higher association between health effects and exposures to ultrafine particles compared to accumulation mode or coarse particles.…”