ROLE OF LEUKOTRIENE-D4 IN THE EARLY AND LATE PULMONARY RESPONSES OF RATS TO ALLERGEN CHALLENGE

To examine the role of leukotriene D4 (LTD4) in early and late pulmonary responses to antigen, we evaluated the effects of two LTD4 antagonists, MK-571 and FPL-57231, on the changes in pulmonary resistance (RL) in the 8-h period following antigen challenge of allergic rats. A total of 69 rats, aged 6 to 8 wk, were sensitized to subcutaneous ovalbumin (OA, 1 mg) and intraperitoneal Bordetella pertussis vaccine (6 x 109 bacilli). At 14 days after sensitization, rats were anesthetized with intraperitoneal urethane (1.1 g/kg) and intubated endotracheally. Aerosols of OA (5% wt/vol in saline for 5 min) were administered to 24 control rats, to 11 rats that were pretreated with aerosolized FPL-57231, and to 8 rats that were pretreated with MK-571; 6 rats also received MK-571 at 2 h after OA. A control group of 13 rats was challenged with aerosols of aline. We defined an early response (ER) as an increase in RL to at least 150% of the postsaline value occurring within 1 h after OA challenge. A late response (LR) was defined as a value of RL exceeding the mean plus 2 SD of all values of RL from 75 min to 8 h after OA challenge and lasting at least 30 min. An ER was observed in 17 of 24 control rats, in 8 of 11 FPL-57231-pretreated rats, and in 3 of 8 MK-571-pretreated rats (not significant). The magnitude and duration of the ER were significantly reduced by MK-571, whereas only the duration was affected by FPL-57231. An LR was observed in 11 of 24 control rats. Rats pretreated with FPL-57231 and MK-571 did not show any significant LR. We conclude that LTD4 is an important mediator of the ER and LR in the Brown-Norway rat.