TY - JOUR
T1 - Ozone exposure and the production of reactive oxygen species by bronchoalveolar cells in humans
AU - Voter, K. Z.
AU - Whitin, J. C.
AU - Torres, A.
AU - Morrow, P. E.
AU - Cox, C.
AU - Tsai, Y.
AU - Utell, M. J.
AU - Frampton, M. W.
N1 - Funding Information:
Supported by contract 91-2 from the Health Effects Institute, and grants RO1HL51701, RO1ES02679, RO1AI19656, RR00044, and ES01247 from the National Institutes of Health. The authors acknowledge the valuable technical assistance of Mitra Azadniv, David Chalupa, Lauren Frasier, F. Raymond Gibb, and Donna Speers. Research described in this article was conducted under contract to the Health Effects Institute (HEI), an organization jointly funded by the U.S. Environmental Protection Agency (EPA) (assistance agreement X-812059) and automotive manufacturer.Ts echon-tents of this article do not necessarily reflect the views of the HEI, nor do they necessarily reflect the policies of the U.S. EPA or of automotive manufacturers.
PY - 2001
Y1 - 2001
N2 - Exposure to ozone injures respiratory epithelium, and the mechanisms may involve the generation of reactive oxygen species (ROS). This study tested the hypothesis that ozone exposure increases the airway burden of ROS to a greater degree in smokers than nonsmokers, and that this effect is independent of ozone-induced changes in spirometry. Healthy subjects were selected as either responders (decrement in FEV1 > 15%) or non-responders (decrement in FEV1 < 5%) to ozone; each underwent 2 exposures to ozone and 1 to air, with bronchoalveolar lavage (BAL) performed 30 min (early) and 18 h (late) after exposure. Release of superoxide anion (O2-) was used as a measure of ROS release by all BAL cells, and flow cytometry was used to detect ROS production in alveolar macrophages (AM) only. Recovery of AM was approximately threefold greater in smokers than nonsmokers. Unstimulated, but not stimulated, cells obtained by BAL from smokers released approximately twofold greater amounts of O2- than cells from nonsmokers, both early and late after ozone exposure (p = .012 and p = .046, respectively). Stimulated, but not unstimulated, ROS generation by AM from smokers increased following ozone exposure, but the ozone effect was not significant. ROS production by AM decreased in nonsmokers (air vs. ozone late, p = .014). Total protein, albumin, and immunoglobulin M (IgM) increased in BAL fluid, consistent with an increase in epithelial permeability. In addition, the concentration of α2-macroglobulin increased approximately threefold 18 h after exposure in nonsmokers (p < .001). No relationship was found between measures of ROS production and lung function responsiveness to ozone. These studies suggest the airways of smokers experience a greater burden of ROS than those of nonsmokers following ozone exposure.
AB - Exposure to ozone injures respiratory epithelium, and the mechanisms may involve the generation of reactive oxygen species (ROS). This study tested the hypothesis that ozone exposure increases the airway burden of ROS to a greater degree in smokers than nonsmokers, and that this effect is independent of ozone-induced changes in spirometry. Healthy subjects were selected as either responders (decrement in FEV1 > 15%) or non-responders (decrement in FEV1 < 5%) to ozone; each underwent 2 exposures to ozone and 1 to air, with bronchoalveolar lavage (BAL) performed 30 min (early) and 18 h (late) after exposure. Release of superoxide anion (O2-) was used as a measure of ROS release by all BAL cells, and flow cytometry was used to detect ROS production in alveolar macrophages (AM) only. Recovery of AM was approximately threefold greater in smokers than nonsmokers. Unstimulated, but not stimulated, cells obtained by BAL from smokers released approximately twofold greater amounts of O2- than cells from nonsmokers, both early and late after ozone exposure (p = .012 and p = .046, respectively). Stimulated, but not unstimulated, ROS generation by AM from smokers increased following ozone exposure, but the ozone effect was not significant. ROS production by AM decreased in nonsmokers (air vs. ozone late, p = .014). Total protein, albumin, and immunoglobulin M (IgM) increased in BAL fluid, consistent with an increase in epithelial permeability. In addition, the concentration of α2-macroglobulin increased approximately threefold 18 h after exposure in nonsmokers (p < .001). No relationship was found between measures of ROS production and lung function responsiveness to ozone. These studies suggest the airways of smokers experience a greater burden of ROS than those of nonsmokers following ozone exposure.
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U2 - 10.1080/08958370151131837
DO - 10.1080/08958370151131837
M3 - Article
C2 - 11445887
AN - SCOPUS:0034956518
SN - 0895-8378
VL - 13
SP - 465
EP - 483
JO - Inhalation Toxicology
JF - Inhalation Toxicology
IS - 6
ER -