EFFECTS OF OZONE ON CYCLOOXYGENASE METABOLITES IN THE BABOON TRACHEOBRONCHIAL TREE

Short-term exposure to 0.5 parts per million (ppm) ozone has been shown to cause an increase in respiratory resistance in primates that can be diminished by 50% with pretreatment with cromolyn sodium. Because of the known membrane-stabilizing effecs of cromolyn and the resultant inhibition of mediator production, we hypothesized a role for the products of arachidonic acid (AA) metabolism in these events. We exposed five adult male baboons to 0.5 ppm ozone on two occasions, once with cromolyn pretreatment and once without. Pulmonary resistance (RL) was monitored and bronchoalveolar (BAL) was performed before and after each exposure. The BAL was analyzed for a stable hydrolysis product of prostacyclin, 6-keto-prostaglandin (PG) F(1α), PGE2, a stable hydrolysis product of thromboxane (Tx) A2, TxB2, and PGF(2α). RL increased after ozone exposure (1.62 ± 0.23 to 3.77 ± 0.51 cmH2O · l-1 · s, difference 2.15; P < 0.02), and this effect was partially blocked by cromolyn (1.93 ± 0.09 to 3.18 ± 0.40 cmH2O · l-1 s, difference 1.25; P < 0.02). The base-line levels of the metabolites of AA in the BAL were as follows (in pg/ml): 6-keto-PGF(1α) 72.78 ± 12.6, PGE2 145.92 ± 30.52, TxB2 52.52 ± 9.56, and PGF(2α) 22.28 ± 5.42. Ozone exposure had no effect on the level of any of these prostanoids (P = NS). These studies quantify the magnitude of cyclooxygenase products of AA metabolism in BAL from baboon lungs and demonstrate that changes in the levels of these mediators in BAL are not prerequisites for ozone-induced increases in respiratory resistance. It will be important to examine the levels of these metabolites as they exist not only in alveolar lavage fluid but in the relevant airways to draw more direct comparisons between the cellular biochemistry and the effect of that biochemistry on gross respiratory mechanics.