Pulmonary inflammatory effects of source-oriented particulate matter from California's San Joaquin Valley.

The EPA regulates ambient particulate matter (PM) because substantial associations have been established between PM and health impacts. Presently, regulatory compliance involves broad control of PM emission sources based on mass concentration rather than chemical composition, although PM toxicity is likely to vary depending upon PM physicochemical properties. The overall objective of this study was to help inform source-specific PM emission control regulations. For the first time, source-oriented PM was collected from the atmosphere in Fresno, CA, onto 38 source/size substrates. Mice were exposed via oropharyngeal aspiration to equivalent mass doses [50 µg] of two size fractions: ultrafine (Dp < 0.17µm) and submicron fine (0.17 < Dp < 1 µm) during summer and winter seasons. At 24 hours post-exposure, cellular and biochemical indicators of pulmonary inflammation were evaluated in the bronchoalveolar lavage fluid. Significant inflammatory responses were elicited by vehicle, regional background, and cooking PM sources that were dependent on season and particle size. This is the first study of source-oriented toxicity of atmospheric PM and supports source-specific emissions control strategies.

Allergic airway inflammation is differentially exacerbated by daytime and nighttime ultrafine and submicron fine ambient particles: heme oxygenase-1 as an indicator of PM-mediated allergic inflammation.

Ambient particulate matter (PM) originates from a range of sources and differs in composition with respect to season, time of day, and particle size. In this study, ambient PM samples in the ultrafine and submicrometer fine range were tested for the potential to exacerbate a murine model of allergic airway inflammation when exposure occurs solely during allergic sensitization, but not during subsequent allergen challenge. Temporally resolved and size-segregated PM samples were used to understand how summer or winter, day or night, and ambient ultrafine and submicrometer fine particle size influence PM's ability to exacerbate allergic inflammation. PM was collected in urban Fresno, CA. BALB/c mice were exposed to PM and house dust mite allergen (HDM) via intranasal aspiration on d 1, 3, and 5. HDM challenge occurred on d 12-14, with inflammation assessed 24 h following final challenge. While season or particle size did not predict allergic inflammation, daytime ultrafine and submicrometer fine particles significantly increased total cellular inflammation, specifically lymphocyte and eosinophil infiltration, compared to allergic controls. Further studies examined PM-mediated changes within the lung during the period where allergen sensitization occurred by measuring direct effects of PM on pulmonary oxidative stress and inflammation. Pulmonary levels of heme oxygenase-1 (HO-1), a biomarker of oxidative stress, but not cellular inflammation, demonstrated a remarkable correlation with the degree of allergic inflammation in animals sensitized to allergen and PM concomitantly, suggesting acute PM-mediated HO-1 levels may serve as a predictive indicator of a particle's ability to exacerbate allergic airway inflammation.

Glutathione (GSH) and the GSH synthesis gene Gclm modulate plasma redox and vascular responses to acute diesel exhaust inhalation in mice.

CONTEXT: Inhalation of fine particulate matter (PM2.5) is associated with acute pulmonary inflammation and impairments in cardiovascular function. In many regions, PM2.5 is largely derived from diesel exhaust (DE), and these pathophysiological effects may be due in part to oxidative stress resulting from DE inhalation. The antioxidant glutathione (GSH) is important in limiting oxidative stress-induced vascular dysfunction. The rate-limiting enzyme in GSH synthesis is glutamate cysteine ligase and polymorphisms in its catalytic and modifier subunits (GCLC and GCLM) have been shown to influence vascular function and risk of myocardial infarction in humans. OBJECTIVE: We hypothesized that compromised de novo synthesis of GSH in Gclm⁻/⁺ mice would result in increased sensitivity to DE-induced lung inflammation and vascular effects. MATERIALS AND METHODS: WT and Gclm⁻/⁺ mice were exposed to DE via inhalation (300 µg/m³) for 6 h. Neutrophil influx into the lungs, plasma GSH redox potential, vascular reactivity of aortic rings and aortic nitric oxide (NO•) were measured. RESULTS: DE inhalation resulted in mild bronchoalveolar neutrophil influx in both genotypes. DE-induced effects on plasma GSH oxidation and acetylcholine (ACh)-relaxation of aortic rings were only observed in Gclm⁻/⁺ mice. Contrary to our hypothesis, DE exposure enhanced ACh-induced relaxation of aortic rings in Gclm⁻/⁺ mice. DISCUSSION AND CONCLUSION: THESE data support the hypothesis that genetic determinants of antioxidant capacity influence the biological effects of acute inhalation of DE. However, the acute effects of DE on the vasculature may be dependent on the location and types of vessels involved. Polymorphisms in GSH synthesis genes are common in humans and further investigations into these potential gene-environment interactions are warranted.