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2630403 
Journal Article 
Abstract 
Systemic and airway biomarkers of inflammation in an elderly panel cohort are related to the potential of airborne particles to generate reactive oxygen species in alveolar macrophage cells in vitro 
Delfino, RJ; Gillen, DL; Tjoa, T; Staimer, N; Arhami, M; Polidori, A; George, SC; Shafer, M; Schauer, JJ; Sioutas, C 
2010 
Yes 
American Journal of Respiratory and Critical Care Medicine
ISSN: 1073-449X
EISSN: 1535-4970 
181 
A1715 
English 
WOS:000208771000715 
is part of a larger document 3452678 Proceedings of the American Thoracic Society 2010 International Conference, May 14-19, 2010, New Orleans
Rationale: We previously found that quasi-ultrafine particulate matter (PM) <0.25 μm in diameter (PM0.25) was associated with increased interleukin-6 (IL-6, a biomarker of systemic inflammation) in an elderly panel cohort. In the same panel, we wished to determine whether pro-inflammatory effects of PM0.25 were reflected by the potential of particles to induce macrophages to produce reactive oxygen species (ROS). Cellular production of ROS induced by PM0.25 was measured using rat alveolar macrophage cells (NR8383). This targets a potential mechanism of PM-induced oxidative stress, namely, the capacity of PM to stimulate cellular generation of ROS.

Methods: Sixty elderly subjects were monitored with 12 weekly measurements of both plasma IL-6 and offline fractional exhaled NO (FeNO, a biomarker of airway inflammation). FeNO was measured using ATS/ERS recommended procedures. PM0.25 was collected daily on filters with impactor samplers. Macrophages were exposed to aqueous extracts of PM0.25 filters collected over 5 days preceding each subject’s biomarker measurement. Fluorescence intensity after the incubation of cells with the PM0.25 extract and the ROS probe DCFH-DA was measured to represent the oxidative generating capacity of particle extracts. Un-opsonized Zymosan served as a positive control because it binds to TLR-2 receptors on macrophage cells and then activates a strong respiratory burst. ROS results are reported in units of Zymosan equivalents. Mixed models were used to analyze the relation of biomarkers to ROS production, adjusted for temperature, season and community.

Results: Both IL-6 and FeNO were significantly positively associated with in vitro ROS production by macrophages exposed to weekly particle extracts. IL-6 increased by 0.21 pg/mL (95% CI: 0.08, 0.34) and FeNO increased by 0.71 ppb (95% CI: 0.09, 1.32) for an interquartile range increase of 35.4 μg Zymosan equivalents/m^3 air. IL-6 was nominally associated with 5-day outdoor mass of PM0.25, but FeNO was not associated with mass. When PM0.25 was regressed with ROS in relation to IL-6, the regression coefficient for PM0.25 was halved whereas the coefficient for ROS activity was reduced by only 10% (PM0.25-ROS rank correlation=0.44).

Conclusion: Results show that the ability of particles to induce ROS generation by macrophages is associated with both systemic and airway biomarkers of inflammation. Co-regression models of PM0.25 with ROS production suggest that oxidative potential explains most of the association of IL-6 with PM0.25 mass. The association of FeNO with ROS activity was not reflected by particle mass concentration. PM mass concentration incompletely reflects the oxidative potential of pollutant particles.

This abstract is funded by: NIH, NIEHS# ES12243; California Air Resources Board # 03-329; US EPA # RD83241301 
American Thoracic Society 2010 International Conference 
New Orleans, LA 
May 14-19, 2010