Recent epidemiological studies have demonstrated associations between air pollution and adverse effects that extend beyond respiratory and cardiovascular disease, including low birth weight, appendicitis, stroke, and neurological/neurobehavioural outcomes (e.g., neurodegenerative disease, cognitive decline, depression, and suicide). To gain insight into mechanisms underlying such effects, we mapped gene profiles in the lungs, heart, liver, kidney, spleen, cerebral hemisphere, and pituitary of male Fischer-344 rats immediately and 24h after a 4-h exposure by inhalation to particulate matter (0, 5, and 50mg/m3 EHC-93 urban particles) and ozone (0, 0.4, and 0.8 ppm). Pollutant exposure provoked differential expression of genes involved in a number of pathways, including antioxidant response, xenobiotic metabolism, inflammatory signalling, and endothelial dysfunction. The mRNA profiles, while exhibiting some interorgan and pollutant-specific differences, were remarkably similar across organs for a set of genes, including increased expression of redox/glucocorticoid-sensitive genes and decreased expression of inflammatory genes, suggesting a possible hormonal effect. Pollutant exposure increased plasma levels of adrenocorticotropic hormone and the glucocorticoid corticosterone, confirming activation of the hypothalamic-pituitary-adrenal axis, and there was a corresponding increase in markers of glucocorticoid activity. Although effects were transient and presumably represent an adaptive response to acute exposure in these healthy animals, chronic activation and inappropriate regulation of the hypothalamic-pituitary-adrenal axis are associated with adverse neurobehavioral, metabolic, immune, developmental, and cardiovascular effects. The experimental data are consistent with epidemiological associations of air pollutants with extrapulmonary health outcomes and suggest a mechanism through which such health effects may be induced.

Air pollution is a risk factor for cardiovascular and respiratory morbidity and mortality. A growing literature also links exposure to diverse air pollutants (e.g., nanoparticles, particulate matter, ozone, traffic-related air pollution) with brain health, including increased incidence of neurological and psychiatric disorders such as cognitive decline, dementia (including Alzheimer's disease), anxiety, depression, and suicide. A critical gap in our understanding of adverse impacts of pollutants on the central nervous system (CNS) is the early initiating events triggered by pollutant inhalation that contribute to disease progression. Recent experimental evidence has shown that particulate matter and ozone, two common pollutants with differing characteristics and reactivity, can activate the hypothalamic-pituitary-adrenal (HPA) axis and release glucocorticoid stress hormones (cortisol in humans, corticosterone in rodents) as part of a neuroendocrine stress response. The brain is highly sensitive to stress: stress hormones affect cognition and mental health, and chronic stress can produce profound biochemical and structural changes in the brain. Chronic activation and/or dysfunction of the HPA axis also increases the burden on physiological stress response systems, conceptualized as allostatic load, and is a common pathway implicated in many diseases. The present paper provides an overview of how systemic stress-dependent biological responses common to particulate matter and ozone may provide insight into early CNS effects of pollutants, including links with oxidative, inflammatory, and metabolic processes. Evidence of pollutant effect modification by non-chemical stressors (e.g., socioeconomic position, psychosocial, noise), age (prenatal to elderly), and sex will also be reviewed in the context of susceptibility across the lifespan.

Metals contained in PM2.5 were found to be associated with acute changes in cardiovascular and respiratory physiology.

Periodic elevation of ambient particulate matter and ozone levels is linked to acute cardiac morbidity and mortality. Increased plasma levels of the potent vasoconstrictor endothelin (ET)-1, a prognostic indicator of cardiac mortality, have been detected in both animal models and humans after exposure to air pollutants. The lungs are the primary source of circulating ET-1, but the direct effects of individual air pollutants and their interaction in modulating the pulmonary endothelin system are unknown. Fischer-344 rats were exposed to particles (0, 5, 50 mg/m3 EHC-93), ozone (0, 0.4, 0.8 ppm), or combinations of particles and ozone for 4 h. Changes in gene expression were measured using real-time reverse transcription polymerase chain reaction immediately after exposure and following 24 h recovery in clean air. Both pollutants individually increased preproET-1, endothelin converting enzyme-1, and endothelial nitric oxide synthase mRNA levels in the lungs shortly after exposure, consistent with the concomitant increase in plasma of the 21 amino acid ET-1[1-21] peptide measured by HPLC-fluorescence. PreproET-1 mRNA remained elevated 24 h after exposure to particles but not after ozone, in line with previously documented changes of the peptide in plasma. Both pollutants transiently increased endothelin-B receptor mRNA expression, while ozone decreased endothelin-A receptor mRNA levels. Coexposure to particles plus ozone increased lung preproET-1 mRNA but not plasma ET-1[1-21], suggesting alternative processing or degradation of endothelins. This coincided with an increase in the lungs of matrix metalloproteinase-2 (MMP-2), an enzyme that cleaves bigET-1 to ET-1[1-32]. Taken together, our data indicate that ozone and particulate matter independently regulate the expression of lung endothelin system genes, but show complex toxicological interaction with respect to plasma ET-1.

The toxicity of carbon nanotubes (CNTs) has received significant attention due to their usage in a wide range of commercial applications. While numerous studies exist on their impacts in water and soil ecosystems, there is a lack of information on the exposure to CNTs from the atmosphere. The transformation of CNTs in the atmosphere, resulting in their functionalization, may significantly alter their toxicity. In the current study, the chemical modification of single wall carbon nanotubes (SWCNTs) via ozone and OH radical oxidation is investigated through studies that simulate a range of expected tropospheric particulate matter (PM) lifetimes, in order to link their chemical evolution to toxicological changes. The results indicate that the oxidation favors carboxylic acid functionalization, but significantly less than other studies performed under nonatmospheric conditions. Despite evidence of functionalization, neither O 3 nor OH radical oxidation resulted in a change in redox activity (potentially giving rise to oxidative stress) or in cytotoxic end points. Conversely, both the redox activity and cytotoxicity of SWCNTs significantly decreased when exposed to ambient urban air, likely due to the adsorption of organic carbon vapors. These results suggest that the effect of gas−particle partitioning of organics in the atmosphere on the toxicity of SWCNTs should be investigated further.