Inhalation of House Dust and Ozone Alters Systemic Levels of Endothelial Progenitor Cells, Oxidative Stress, and Inflammation in Elderly Subjects
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In: Toxicological sciences , Vol. 163, No. 2, 01.06.2018, p. 353-363.
Research output: Contribution to journal › Article › peer-review
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T1 - Inhalation of House Dust and Ozone Alters Systemic Levels of Endothelial Progenitor Cells, Oxidative Stress, and Inflammation in Elderly Subjects
AU - Jantzen, Kim
AU - Jensen, Annie
AU - Kermanizadeh, Ali
AU - Elholm, Grethe
AU - Sigsgaard, Torben
AU - Møller, Peter
AU - Roursgaard, Martin
AU - Loft, Steffen
PY - 2018/6/1
Y1 - 2018/6/1
N2 - Ambient air pollution including ozone and especially particulate matter represents important causes of cardiovascular disease. However, there is limited knowledge on indoor air dust with respect to this risk and the potential interactions between dust and ozone. Here, we exposed 23 healthy elderly subjects for 5.5 h, to either clean air, house dust at 275 µg/m3 (diameter < 2.5 µm), ozone at 100 ppb or combined house dust and ozone in a double-blinded randomized cross-over study. The combined house dust and ozone exposure was associated with a 48% (95% CI 24%-65%) decrease as compared with the clean air exposure, in CD34+KDR+ late endothelial progenitor cells (EPCs) per leukocyte in the blood shortly after exposure, whereas none of the single exposures resulted in a significant effect. The combined exposure also increased reactive oxygen species production capacity in granulocytes and monocytes as well as an up-regulation of interleukin-8 mRNA levels in leukocytes. Ozone alone reduced the gene expression of tumor necrosis factor and C-C motif chemokine ligand 2, while dust alone showed no effects. The combined exposure to house dust and ozone also reduced levels of oxidized purines in DNA consistent with concomitant up-regulation of mRNA of the repair enzyme 8-oxoguanine DNA glycosylase. The reduction in late EPCs can be an indicator of cardiovascular risk caused by the combination of pulmonary oxidative stress induced by ozone and the inflammatory potential of the house dust. These data were corroborated with in vitro findings from exposed human macrophages and endothelial cells.
AB - Ambient air pollution including ozone and especially particulate matter represents important causes of cardiovascular disease. However, there is limited knowledge on indoor air dust with respect to this risk and the potential interactions between dust and ozone. Here, we exposed 23 healthy elderly subjects for 5.5 h, to either clean air, house dust at 275 µg/m3 (diameter < 2.5 µm), ozone at 100 ppb or combined house dust and ozone in a double-blinded randomized cross-over study. The combined house dust and ozone exposure was associated with a 48% (95% CI 24%-65%) decrease as compared with the clean air exposure, in CD34+KDR+ late endothelial progenitor cells (EPCs) per leukocyte in the blood shortly after exposure, whereas none of the single exposures resulted in a significant effect. The combined exposure also increased reactive oxygen species production capacity in granulocytes and monocytes as well as an up-regulation of interleukin-8 mRNA levels in leukocytes. Ozone alone reduced the gene expression of tumor necrosis factor and C-C motif chemokine ligand 2, while dust alone showed no effects. The combined exposure to house dust and ozone also reduced levels of oxidized purines in DNA consistent with concomitant up-regulation of mRNA of the repair enzyme 8-oxoguanine DNA glycosylase. The reduction in late EPCs can be an indicator of cardiovascular risk caused by the combination of pulmonary oxidative stress induced by ozone and the inflammatory potential of the house dust. These data were corroborated with in vitro findings from exposed human macrophages and endothelial cells.
KW - Air Pollution, Indoor/adverse effects
KW - Cross-Over Studies
KW - Double-Blind Method
KW - Dust/analysis
KW - Endothelial Progenitor Cells/cytology
KW - Healthy Volunteers
KW - Humans
KW - Inflammation/blood
KW - Inhalation Exposure/adverse effects
KW - Interleukin-8/blood
KW - Leukocytes/immunology
KW - Oxidative Stress/drug effects
KW - Ozone/toxicity
KW - Particle Size
U2 - 10.1093/toxsci/kfy027
DO - 10.1093/toxsci/kfy027
M3 - Article
C2 - 29767793
VL - 163
SP - 353
EP - 363
JO - Toxicological sciences
JF - Toxicological sciences
SN - 1096-0929
IS - 2
ER -