POTENTIAL INVOLVEMENT OF 4-HYDROXYNONENAL IN THE RESPONSE OF HUMAN LUNG-CELLS TO OZONE

Ozone is a photochemically generated pollutant that can cause acute pu lmonary inflammation and induce cellular injury and may contribute to the development or exacerbation of chronic lung diseases. Despite much research, the mechanisms of ozone-and oxidant-induced cellular injury are still uncertain. Ozone and secondary free radicals have been repo rted to cause the formation of aldehydes in biological fluids. One of the most toxic aldehydes formed during oxidant-induced lipid peroxidat ion is 4-hydroxynonenal (HNE). HNE reacts primarily with Cys, Lys, and His amino acids, altering protein function and forming protein adduct s. The purpose of this study was to determine whether HNE could accoun t for the acute effects of ozone on lung cells. Human subjects were ex posed to 0.4 parts/million ozone or air for 1 h with exercise (each su bject served as his/her own control). Six hours after ozone exposure, cells obtained by airway lavage were examined for apoptotic cell injur y, and cells from bronchoalveolar lavage were examined for apoptosis, presence of HNE adducts, and expression of stress proteins. Significan t apoptosis was evident in airway lung cells after ozone exposure. Wes tern analysis demonstrated an increase in a 32-kDa HNE protein adduct and a number of stress proteins, viz., 72-kDa heat shock protein and f erritin, in alveolar macrophages (AM) after ozone exposure. All of the se effects could be replicated by in vitro exposure of AM to HNE. Cons equently, the in vitro results and demonstration of HNE protein adduct s after ozone exposure are consistent with a potential role for HNE in the cellular toxic effects of ozone.