title: Murine pulmonary inflammatory responses following instillation of size-fractionated ambient particulate matter.
abstract: 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 microm), fine (FI; 1.7-3.5 microm), and fine/ultrafine (FU; <1.7 microm) 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 10, 50, or 100 microg 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 ni change in lactate dehydrogenase (LDH) activity, and increased albumin and tumor necrosis factor (TNF)-alpha levels were only seen with the high-dose FI particles. Interleukin 6 (IL-6) levels were increased over control levels after treatment with 100 microg of all 3 particle sizes. To determine whether oxidative stress may contribute to these effects, antioxidant levels in the ling 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 the 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.
authors.affiliation: Center for Environmental Medicine and Lung Biology, University of North Carolina, Chapel Hill, USA.
authors.forename: Colin A J
authors.initials: CA
authors.lastname: Dick
authors.forename: Pramila
authors.initials: P
authors.lastname: Singh
authors.forename: Mary
authors.initials: M
authors.lastname: Daniels
authors.forename: Paul
authors.initials: P
authors.lastname: Evansky
authors.forename: Susanne
authors.initials: S
authors.lastname: Becker
authors.forename: M Ian
authors.initials: MI
authors.lastname: Gilmour
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D016207:Cytokines / Q000032:analysis; D005260:Female; D008168:Lung / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D020556:Neutrophil Infiltration; D018384:Oxidative Stress; D010316:Particle Size; D011014:Pneumonia / Q000209:etiology* / Q000662:veterinary
chemical_list: D000393:Air Pollutants; D016207:Cytokines