Epidemiological studies demonstrated an association between increased levels of ambient air pollution particles and human morbidity and mortality. Production of oxidants, either directly by the air pollution particles or by the host response to the particles, appears to be fundamental in the biological effects seen after exposure to particulate matter (PM). However, the precise components and mechanisms responsible for oxidative stress following PM exposure are yet to be defined. Direct oxidant generation by air pollution particles is attributed to organic and metal components. Organic compounds generate an oxidative stress through redox cycling of quinone-based radicals, by complexing of metal resulting in electron transport, and by depletion of antioxidants by reactions between quinones and thiol-containing compounds. Metals directly support electron transport to generate oxidants and also diminish levels of antioxidants. In addition to direct generation of oxidants by organic and metal components, cellular responses contribute to oxidative stress after PM exposure. Reactive oxygen species (ROS) production occurs in the mitochondria, cell membranes, phagosomes, and the endoplasmic reticulum. Oxidative stress following PM exposure initiates a series of cellular reactions that includes activation of kinase cascades and transcription factors and release of inflammatory mediators, which ultimately lead to cell injury or apoptosis. Consequently, oxidative stress in cells and tissues is a central mechanism by which PM exposure leads to injury, disease, and mortality.

Epidemiologic investigation has established an association between exposure to particulate matter (PM) and human health in the Utah Valley. Reduction of particle mass during the temporary closure of a local steel mill was associated with diminished morbidity and mortality. We tested the hypothesis that the biologic effect of PM would reflect findings of epidemiology with a greater injury after exposure to an equal mass of particles from those years in which the mill was in operation. Filters containing PM were collected prior to closure of the steel mill, during the closure, and after its reopening. Aqueous extracts of the filters were prepared. One of three extracts (500 μ g) was instilled through the bronchoscope into the lungs of nonsmoking volunteers. Twenty-four hours later, the same subsegment was lavaged. Exposure to aqueous extracts of PM collected before closure and after reopening of the steel mill provoked a greater inflammatory response relative to PM extract acquired during the plant shutdown. This is the first demonstration that pulmonary effects after experimental exposure of humans to PM can correlate with health outcomes observed in epidemiologic studies of the same material under normal exposure conditions. Findings suggest that mass may not be the most appropriate metric to use in assessing health effects after PM exposure but rather specific components must be identified and assessed.

Rationale: Lung injury after cigarette smoking is related to particle retention. Iron accumulates with the deposition of these particles. Objectives: We tested the postulate that (1) injury after smoking correlates with exposure to the particulate fraction of cigarette smoke, (2) these particles alter iron homeostasis, triggering metal accumulation, and (3) this alteration in iron homeostasis affects oxidative stress and inflammation. Methods: Rats and human respiratory epithelial cells were exposed to cigarette smoke, filtered cigarette smoke, and cigarette smoke condensate (the particulate fraction of smoke), and indices of iron homeostasis, oxidative stress, and inflammatory injury were determined. Comparable measures were also evaluated in nonsmokers and smokers. Measurements and Main Results: After exposure of rats to cigarette smoke, increased lavage concentrations of iron and ferritin, serum ferritin levels, and nonheme iron concentrations in the lung and liver tissue all increased. Lavage ascorbate concentrations were decreased, supporting an oxidative stress. After filtering of the cigarette smoke to remove particles, most of these changes were reversed. Exposure of cultured respiratory epithelial cells to cigarette smoke condensate caused a similar accumulation of iron, metal-dependent oxidative stress, and increased IL-8 release. Lavage samples in healthy smokers and smoking patients with chronic obstructive pulmonary disease revealed elevated concentrations of both iron and ferritin relative to healthy nonsmokers. Lavage ascorbate decreased with cigarette smoking. Serum iron and ferritin levels among smokers were increased, supporting systemic accumulation of this metal after cigarette smoke exposure. Conclusions: We conclude that cigarette smoke particles alter iron homeostasis, both in the lung and systemically.

Environmental Health Perspectives is an Open Access journal published by the National Institute of Environmental Health Sciences. Environmental Health Perspectives is an Open Access journal published by the National Institute of Environmental Health Sciences.

Descriptions of changes in hematological indices have contested the premise that the biological effects of suspended particulate matter (PM) are restricted to the lung. Employing approximately 40 hematologic parameters reflecting blood cells, chemistries, mediators, and coagulation factors, we tested the hypothesis that exposure to concentrated ambient air particles (CAPs) can be associated with changes in hematologic indices in normal humans. Twenty healthy young volunteers were exposed to either filtered air (n = 5) or CAPs (n = 15) with a mean PM mass of 120.5 ± 14.0 µg/m³ and a range from 15.0–357.6 µg/m³. Hematologic indices were measured. Changes in all parameters are expressed as the absolute value either immediately after or 24 h after exposure. Differences between responses of those individuals exposed to filtered air and CAPs were tested using the T-test of independent means. If significant differences between the two groups were suggested by the T-test (p < .10), the relationship was further evaluated employing linear regression techniques. Regression analysis verified significant linear relationships between particle mass the individual was exposed to and (1) decrements in WBC count 24 h later, (2) decreases in lactate dehydrogenase (LDH) concentration 24 h later, and (3) elevations in fibrinogen levels 24 h later. There were no changes in either inflammatory mediators in the blood or indices of coagulation/fibrinolysis other than fibrinogen. We conclude that exposure of healthy volunteers to CAPs can be associated with decreases of both white blood cell (WBC) count and LDH and increased concentrations of fibrinogen in the blood.