Project at a Glance
Title: Effects of serial-day exposure to nitrogen dioxide on airway and blood leukocytes and lymphocyte sub-sets.
Principal Investigator / Author(s): Balmes, John R
Contractor: UC San Francisco
Contract Number: 93-317
Research Program Area: Health & Exposure
Topic Areas: Ambient Air Quality Stds, Health Effects of Air Pollution
Nitrogen dioxide (NO2 is a free radical and oxidant gas present in both indoor and outdoor air. Inhalation of NO2 could cause airway inflammation, and also decrease local or systemic immune function by changing the distribution of lymphocyte subsets, or inhibiting lymphocyte activation. This experiment was designed to test the hypothesis that exposure to NO2 would: 1) increase leukocytes in bronchoalveolar lavage BAL), 2) change the distribution of lymphocyte subsets and inhibit lymphocyte activation in BAL and peripheral blood (PB; and 3) increase proteins in BAL. Within a counter-balanced, repeated measures design, 15 healthy volunteers (x ±SD: age = 29.2 ± 4.8 yr; FEV, = 4.38 ± 0.8 1) were exposed to filtered air (FA) or 2.0 ppm NO2 for four hours per day, alternating 30-mininute periods of rest and exercise, for three consecutive days. Bronchoscopy was performed I8 hours following each exposure set, and PB was drawn immediately pre-exposure, and pre-bronchoscopy. Flow cytometry was used to enumerate B cells (CD19+), T-helper cells (CD3+CD4+), T-suppressor cells (CD3+CD8+), and NK cells (CD3-CD16+CD56+), and to examine the expression of the activation markers CD25 and CD69, on T and NK cells in both BAL and PB. In the Bronchial Fraction [(BFx), defined as the first I5 ml of BAL collected], there was an increase in percent neutrophils following NO2 exposure compared to FA [median (range): 10.6 (2.2-43.6)% vs 5.3 (l.0-14.3)%; P=0.005]. There were no between condition differences for BAL or BFx in total leukocyte count, or percent of macrophages, eosinophils, lymphocytes or neutrophils. In BAL, there was a significant decrease in the percent of T-helper cells following NO2 exposure compared to FA [median (range): 55.9 (29.2-73.9)% vs 61.6 (42.0-85.9)%; P=0.022]. For BAL and PB, there were no other significant, between- or within-exposure differences in any lymphocyte subsets, or in lymphocyte sub-set activation. In the BFx, there was a decrease in total protein following NO2 exposure compared to FA [median (range}: 0.117 (0.054-0.225) mg ml vs 0.171 (0.068-0.538) mg ml; P=0.004]. There were no between condition differences in the BAL total protein, or the BFx or BAL lactate dehydrogenase. We conclude that serial-day exposure to 2.0 ppm NO2 results in bronchial inflammation and a minimal change in a BAL lymphocyte subset, with no changes in PB lymphocyte subsets or activation.
For questions regarding this research project, including available data and progress status, contact: Heather Choi at (916) 322-3893
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