Release of prostaglandin E2 and leukotriene C4/D4 from airway segments isolated from rats after exposure to ozone for 20 months.
Metabolites of arachidonic acid have been implicated as mediators of some of the pulmonary effects observed after acute exposure to ozone. Accordingly, recent studies have focused on the effects of acute ozone exposure on the arachidonic acid cascade, however, whether eicosanoid metabolism is altered after chronic exposure to ozone is unknown. To begin to address this issue, we examined the effects of near-lifetime exposure to ozone on release of prostaglandin E2 (PGE2) and leukotriene C4/D4 from airway segments isolated from exposed Fischer-344 rats. Airway segments representing approximately eighth to tenth generation airways were isolated from rats of both genders that had been exposed for 6 h per day, 5 days per week for 20 months to filtered air or 0.12, 0.5 or 1.0 parts per million (ppm) ozone. Basal and stimulated release of eicosanoids were measured in the medium surrounding airway segments using enzymoimmunoassay. Basal release of PGE2 was detected in the medium surrounding airway segments and this release was unaffected by ozone exposure. Incubation of the segments with the calcium ionophore, A23187, increased the release of the prostaglandin; the A23187-induced release of PGE2 was significantly enhanced in airway segments isolated from rats in the 1.0 ppm exposure group. Basal release of leukotriene C4/D4 was not detected in the medium surrounding airway segments regardless of ozone exposure. Measurable amounts of the leukotriene were released during incubation with A23187, however, ozone was without affect on these levels. The results suggest that the cyclooxygenase pathway of the arachidonic acid cascade appears to be affected by ozone exposure. Which of the processes of prostaglandin production and release are affected by chronic ozone exposure remains to be determined.
Szarek
J L
JL
Department of Pharmacology, Marshall University School of Medicine, Huntington, WV 25704-9388, USA.
Valentovic
M A
MA
D000280:Administration, Inhalation; D000704:Analysis of Variance; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism*; D005260:Female; D007124:Immunoenzyme Techniques; D017997:Leukotriene C4 / Q000378:metabolism*; D017998:Leukotriene D4 / Q000378:metabolism*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D010126:Ozone / Q000008:administration & dosage / Q000633:toxicity*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344
D016718:Arachidonic Acid; D017997:Leukotriene C4; D000001:Calcimycin; D010126:Ozone; D017998:Leukotriene D4; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone