Effects of ozone on nasal mucosa (endothelial cells).

After exposure to ozone, humans develop neutrophil infiltration of the nasal mucosa. To investigate the events contributing to inflammatory cell recruitment in the nasal mucosa we exposed 10 healthy nonsmoking volunteers to 400 ppb ozone or filtered air for 2h at rest on two separate occasions. Nasal biopsies were performed 6h after ozone/filtered air exposure. The nasal 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-1ß, 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, eosinophils, macrophages, 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-1ß (p=0.009), and NF-κB (p=0.05) increased significantly after ozone exposure as compared to 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 neutrophil inflitration in the nasal mucosa.

Effects of ozone on the nasal mucosa (epithelial cells).

Ozone is a significant public health concern worldwide. Despite increasing evidence for the role of the bronchial epithelial cells in the generation of proinflammatory cytokines there is little information on the biological relevance of ozone induced release of cytokines in nasal airway inflammation. We have investigated the effect of ozone on the nasal mucosa using immunohistochemical staining of nasal biopsies taken 6h after exposure to either 400 ppb ozone or filtered. We found that ozone significantly increases the number of neutrophils in the epithelium (p=0.03), and expression of NF-kB (p<0.03), TNF-a (p<0.05), IL-1b (p<0.03), IL-8 (p<0.007), IL-6 (p<0.02), GM-CSF (p<0.02) and ICAM-1 (p <0.01) in the epithelial cells 6h after exposure. Furthermore, we found a significant correlations between IL-8 expression and number of neutrophils (r=0.85, p< 0.002) and NF-kB and TNF-a expression (r=0.77, p<0.009) in the epithelium. These results suggest that ozone-induced inflammation of the nasal mucosa may be a consequence of increased synthesis and release of epithelial cell-derived cytokines and adhesion molecules which influence the activity of inflammatory cells.