ABSTRACT
Normal individuals developed pulmonary neutrophilic inflammation and increased blood fibrinogen following inhalation of concentrated ambient particles (CAPS). In this study, we sought to determine how soluble components in CAPS contributed to these changes. We expanded and reanalyzed data from 37 young healthy volunteers from a previous study (Ghio et al., 2000) who were exposed to either filtered air or CAPS. Postexposure bronchoalveolar lavage (BAL) as well as pre- and postexposure venous blood samples was analyzed for cellular and acute inflammatory endpoints. Nine most abundant components in the water-soluble fraction of CAPS were correlated with these endpoints using principal component analysis. We found that a sulfate/Fe/Se factor was associated with increased BAL percentage of neutrophils and a Cu/Zn/V factor with increased blood fibrinogen. The concentrations of sulfate, Fe, and Se correlated highly with PM mass (R > 0.75) while the correlations between PM and Cu/Zn/V were modest (R = 0.2-0.6). These results from controlled human exposure linked specific PM components to pulmonary neutrolphil influx and blood fibrinogen increase, and indicated the soluble components of pollutant particles may differentially affect pulmonary and hematological systems in humans exposed to PM.
Subject(s)
Air Pollutants/adverse effects , Air Pollutants/analysis , Bronchoalveolar Lavage/methods , Ferritins/blood , Fibrinogen/drug effects , Lung Diseases/blood , Lung Diseases/chemically induced , Particle Size , Adult , Arsenic/analysis , Blood Platelets/chemistry , Copper/analysis , Female , Fibrinogen/chemistry , Fibronectins/chemistry , Humans , Iron/analysis , Lead/analysis , Male , Neutrophils/chemistry , Nickel/analysis , North Carolina , Selenium/analysis , Sulfates/analysis , Vanadium/analysis , Zinc/analysisABSTRACT
The iron chelator deferoxamine has been reported to inhibit both xanthine oxidase (XO) and xanthine dehydrogenase activity, but the relationship of this effect to the availability of iron in the cellular and tissue environment remains unexplored. XO and total xanthine oxidoreductase activity in cultured V79 cells was increased with exposure to ferric ammonium sulfate and inhibited by deferoxamine. Lung XO and total xanthine oxidoreductase activities were reduced in rats fed an iron-depleted diet and increased in rats supplemented with iron, without change in the ratio of XO to total oxidoreductase. Intratracheal injection of an iron salt or silica-iron, but not aluminum salts or silica-zinc, significantly increased rat lung XO and total xanthine oxidoreductase activities, immunoreactive xanthine oxidoreductase, and the concentration of urate in bronchoalveolar fluid. These results suggest the possibility that the production of uric acid, a major chelator of iron in extracellular fluid, is directly influenced by iron-mediated regulation of the expression and/or activity of its enzymatic source, xanthine oxidase.