OZONE-INDUCED INCREASES IN SUBSTANCE-P AND 8-EPI-PROSTAGLANDIN-F(2-ALPHA) IN THE AIRWAYS OF HUMAN-SUBJECTS

We are interested in the mechanisms of ozone-induced lung effects afte r short-term exposure and the relationship with subsequent pulmonary i nflammation and disease. Our hypothesis is that ozone, as a powerful o xidant, will diminish the activity of neutral endopeptidase (NEP) in t he airways of humans with resulting increased concentrations of neurop eptides such as substance P (SP). We have exposed seven (two women, fi ve men) healthy, nonsmoking individuals (22 to 30 yr of age) to filter ed air and ozone (0.25 ppm) for 1 h in an environmental chamber during heavy exercise. Bronchoscopy with airway lavage (AL) and bronchoalveo lar lavage (BAL) was performed immediately after ozone exposure. The l avage samples were analyzed by enzyme immunoassay for SP and 8-epi-pro staglandin F2alpha (8-epi-PGF2alpha) (a marker for oxidative free radi cal reaction) and by radioimmunoassay for complement fragments. FEV1 h ad declined 12.4 +/-1.9% (mean +/- SEM) as a result of ozone exposure. The AL concentration for SP and 8-epi-PG2alpha and BAL concentration of C3a after ozone exposure were significantly higher than after the f iltered air exposure (P < 0.05). There was a significant correlation b etween SP and 8-epi-PGF2alpha concentrations in the AL fluid (r2 = 0.8 9 and P < 0.05). There were no changes in C5a in either compartment or any of the mediators in the plasma samples. These results extend prev ious results from animal studies suggesting that ozone's mechanism of action is through an oxidative reaction resulting in a decreased activ ity of NEP in the airways with a subsequent increase in the concentrat ion and activity of SP.