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 acid (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 nature and biological activity of O3-exposed AA, we exposed AA in a cell-free, aqueous environment to air, 0.1 ppm O3, or 1.0 ppm O3 for 30-120 min. AA exposed to air was not degraded. All O3 exposures degraded > 98% of the AA to more polar products, which were predominantly aldehydic substances (as determined by reactivity with 2,4-dinitrophenylhydrazine and subsequent separation by HPLC) and hydrogen peroxide. The type and amount of aldehydic substances formed depended on the O3 concentration and exposure duration. A human bronchial epithelial cell line (BEAS-2B, S6 subclone) exposed in vitro to either 0.1 ppm or 1.0 ppm O3 for 1 hr produced AA-derived aldehydic substances, some of which eluted with similar retention times as the aldehydic substances derived from O3 degradation of AA in the cell-free system. In vitro, O3-degraded AA induced an increase in human peripheral blood polymorphonuclear leukocyte (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 substances, but not hydrogen peroxide, appeared to be the principal active agents responsible for the observed effects. O3-degraded AA may play a role in the PMN influx into lungs and in decreased T-lymphocyte mitogenesis and natural killer cell activity observed in humans and rodents exposed to O3.
Madden
M C
MC
Center for Environmental Medicine and Lung Biology, University of North Carolina, Chapel Hill 27599.
Friedman
M
M
Hanley
N
N
Siegler
E
E
Quay
J
J
Becker
S
S
Devlin
R
R
Koren
H S
HS
D000447:Aldehydes / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism* / Q000494:pharmacology; D001980:Bronchi / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D055598:Chemical Phenomena; D002621:Chemistry; D006801:Humans; D009504:Neutrophils / Q000187:drug effects; D010126:Ozone / Q000494:pharmacology*
D000447:Aldehydes; D016718:Arachidonic Acid; D010126:Ozone