Murine pulmonary inflammatory responses following instillation of size-fractionated ambient particulate matter

The mechanisms for increased cardiopulmonary disease in individuals exposed to particulate air pollution are associated with fine and ultrafine particles that have a high oxidative potential. Particulate matter (PM) from Research Triangle Park (NC) was collected and separated into 3 different size fractions: coarse (CO; >3.5 mum), fine (FI; 1.7-3.5 mum), and fine/ultrafine (FU, <1.7 mu m) using impaction and electrostatic precipitation. Particle chemistry indicated the presence of sulfates, zinc, iron, and copper in all fractions. CD1 mice were intratracheally instilled with 70, 50, or 100 mu g of each fraction. After 18 h, the lungs were lavaged and assayed for signs of inflammation. All particles produced increases in neutrophil number, and this was highest in the high-dose FU group. Biochemical analysis revealed no change in lactate dehydrogenase (LDH) activity, and increased albumin and tumor necrosis factor (TNF)-alpha levels were only seen with the high-dose Fl particles. Interleukin 6 (IL-6) levels were increased over control levels after treatment with 100 mu g of all 3 particle sizes. To determine whether oxidative stress may contribute to these effects, antioxidant levels in the lung were boosted by an intraperitoneal (ip) injection with dimethylthiourea (DMTU). This treatment resulted in a twofold increase in the total antioxidant capacity of the lung and decreased the PM-induced cytokine and neutrophil influx up to 50%. The data indicate that on an equal mass basis, ambient particles of these three size ranges produce pulmonary inflammation, and that increasing the antioxidant capacity of the lung reduces particle-induced cytokine and cellular responses.