Ozone induces neutrophyl inflammation in the lower airways

After exposure to ozone, humans develop neutrophilic infiltration of the nasal and bronchial mucosa. To investigate the events contributing to inflammatory cell recruitment in the bronchial mucosa we exposed 10 healthy nonsmoking volunteers to 400 ppb ozone or filtered air for 2h at rest on two separate occasions. Bronchial biopsies were performed 6h after ozone/filtered air exposure. The biopsies were embedded in glycol mathacrylate and immunostained for inflammatory cells, including neutrophils, mast cells, total T-cells (CD3), T-cell subsets CD8 and CD4, macrophages, eosinophils, adhesion molecules (P-selectin, E-selectin, ICAM-1, VCAM-1), cytokines (TNF-α, IL-1β, GM-CSF, IL-6), chemokines (IL-8 and RANTES), and nuclear factor NF-κB. No significant changes were seen in the number of T-cells and T-cell subsets, macrophages, eosinophils or percentages of vessels expressing P-selectin, VCAM-1, GM-CSF, IL-6 and RANTES in the biopsies. The number of neutrophils and mast cells in the submucosa was significantly higher after ozone exposure (p=0.009 and p=0.005 respectively). The percentage of vessels expressing E-selectin (p=0.01), ICAM-1 (p=0.005), IL-8 (p=0.02), TNF-α (p=0.02), IL-1β (p=0.009), and NF-κB (p=0.05) increased significantly after ozone exposure versus filtered air exposure. Exposure of normal subjects to ozone increases the expression of proinflammatory cytokines resulting in upregulation of IL-8 and adhesion molecules via activation of NF-κB, leading to neutrophilic infiltration in the bronchial mucosa.