Browsing by Author "Soukup, Joleen M"
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Item Open Access Deficiency of α-1-antitrypsin influences systemic iron homeostasis.(Int J Chron Obstruct Pulmon Dis, 2013) Ghio, Andrew J; Soukup, Joleen M; Richards, Judy H; Fischer, Bernard M; Voynow, Judith A; Schmechel, Donald EThere is evidence that proteases and antiproteases participate in the iron homeostasis of cells and living systems. We tested the postulate that α-1 antitrypsin (A1AT) polymorphism and the consequent deficiency of this antiprotease in humans are associated with a systemic disruption in iron homeostasis. Archived plasma samples from Alpha-1 Foundation (30 MM, 30 MZ, and 30 ZZ individuals) were analyzed for A1AT, ferritin, transferrin, and C-reactive protein (CRP). Plasma samples were also assayed for metals using inductively coupled plasma atomic emission spectroscopy (ICPAES). Plasma levels of A1AT in MZ and ZZ individuals were approximately 60% and 20% of those for MM individuals respectively. Plasma ferritin concentrations in those with the ZZ genotype were greater relative to those individuals with either MM or MZ genotype. Plasma transferrin for MM, MZ, and ZZ genotypes showed no significant differences. Linear regression analysis revealed a significant (negative) relationship between plasma concentrations of A1AT and ferritin while that between A1AT and transferrin levels was not significant. Plasma CRP concentrations were not significantly different between MM, MZ, and ZZ individuals. ICPAES measurement of metals confirmed elevated plasma concentrations of nonheme iron among ZZ individuals. Nonheme iron concentrations correlated (negatively) with levels of A1AT. A1AT deficiency is associated with evidence of a disruption in iron homeostasis with plasma ferritin and nonheme iron concentrations being elevated among those with the ZZ genotype.Item Open Access Seasonal variations in air pollution particle-induced inflammatory mediator release and oxidative stress.(Environmental health perspectives, 2005-08) Becker, Susanne; Dailey, Lisa A; Soukup, Joleen M; Grambow, Steven C; Devlin, Robert B; Huang, Yuh-Chin THealth effects associated with particulate matter (PM) show seasonal variations. We hypothesized that these heterogeneous effects may be attributed partly to the differences in the elemental composition of PM. Normal human bronchial epithelial (NHBE) cells and alveolar macrophages (AMs) were exposed to equal mass of coarse [PM with aerodynamic diameter of 2.5-10 microm (PM(2.5-10)], fine (PM(2.5)), and ultrafine (PM(<0.1)) ambient PM from Chapel Hill, North Carolina, during October 2001 (fall) and January (winter), April (spring), and July (summer) 2002. Production of interleukin (IL)-8, IL-6, and reactive oxygen species (ROS) was measured. Coarse PM was more potent in inducing cytokines, but not ROSs, than was fine or ultrafine PM. In AMs, the October coarse PM was the most potent stimulator for IL-6 release, whereas the July PM consistently stimulated the highest ROS production measured by dichlorofluorescein acetate and dihydrorhodamine 123 (DHR). In NHBE cells, the January and the October PM were consistently the strongest stimulators for IL-8 and ROS, respectively. The July PM increased only ROS measured by DHR. PM had minimal effects on chemiluminescence. Principal-component analysis on elemental constituents of PM of all size fractions identified two factors, Cr/Al/Si/Ti/Fe/Cu and Zn/As/V/Ni/Pb/Se, with only the first factor correlating with IL-6/IL-8 release. Among the elements in the first factor, Fe and Si correlated with IL-6 release, whereas Cr correlated with IL-8 release. These positive correlations were confirmed in additional experiments with PM from all 12 months. These results indicate that elemental constituents of PM may in part account for the seasonal variations in PM-induced adverse health effects related to lung inflammation.