CHEMICAL NATURE AND IMMUNOTOXICOLOGICAL PROPERTIES OF ARACHIDONIC-ACID DEGRADATION PRODUCTS FORMED BY EXPOSURE TO OZONE

Ozone (O3) exposure in vivo has been reported to degrade arachidonic a cid (AA) in the lungs of rodents. The O3-degraded AA products may play a role in the responses to this toxicant. To study the chemical natur e and biological activity of O3-exposed AA, we exposed AA in a cell-fr ee, aqueous environment to air, 0.1 ppm O3, or 1.0 ppm O3 for 30-120 m in. AA exposed to air was not degraded. All 03 exposures degraded >98% of the AA to more polar products, which were predominantly aldehydic substances (as determined by reactivity with 2,4-dinitrophenylhydrazin e and subsequent separation by HPLC) and hydrogen peroxide. The type a nd amount of aldehydic substances formed depended on the 03 concentrat ion and exposure duration. A human bronchial epithelial cell line (BEA S-2B, S6 subclone) exposed in vitro to either 0.1 ppm or 1.0 ppm 03 fo r 1 hr produced AA-derived aldehydic substances, some of which eluted with similar retention times as the aldehydic substances derived from 03 degradation of AA in the cell-free system. In vitro, O3-degraded AA induced an increase in human peripheral blood polymorphonuclear leuko cyte (PMN) polarization, decreased human peripheral blood T-lymphocyte proliferation in response to mitogens, and decreased human peripheral blood natural killer cell lysis of K562 target cells. The aldehydic s ubstances, but not hydrogen peroxide, appeared to be the principal act ive agents responsible for the observed effects. O3-degraded AA may pl ay a role in the PMN influx into lungs and in decreased T-lymphocyte m itogenesis and natural killer cell activity observed in humans and rod ents exposed to O3.