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Summary

The involvement of platelet activating factor (PAF) in antigen-induced bronchial hyperresponsiveness was investigated by the use of the PAF antagonists BN 52021 and BN 50730, in a guinea-pig model where sensilization and challenge were performed by aerosol. Male Hartley guinea-pigs were sensitized by two aerosol exposures at 48 hr intervals to a 0.9% NaCl solution (saline) containing 2 mg/ml ovalbumin lor 30 min. Fifteen to 20 days later, guinea-pigs were challenged by exposure to five successive aerosols ofincreasing concentrations of ovalbumin (OA) or respectively, 10 μg ml. KM) μ/ml, 1 mg/ml. 5 mg/ml and 10 mg/ml for 15 min each, orsaline alone. Three to four hr and 18-24 hr after the aerosol challenge the guinea-pigs were prepared for recording of bronchopulmonary response and aerosol administrations were then generated with an ultrasonic nebulizer. The bronchopulmonary responses induced by successive I-min aerosol bursts of acetylcholine(ACh) was assessed. As compared with saline-challenged guinea-pigs, an enhanced bronchopulmonary response to aerosol administration of cumulative doses of ACh was observed, 3 4 hr and 18 24 hr post-ovalbumin challenge. When the sensitized guinea-pigs were pretreated I hr before ovalbumin exposure with BN 52021 or BN 50730 (25 mg/kg, per ox), a significant inhibition of the increase in the bronchopulmonary response to ACh was observed, both at 3–4 hr and 18–24 hr. Furthermore, when guinea-pigs were treated 3–4 hr after the ovalbumin exposure with BN 52021 or BN 50730, a significant inhibition of the hyperresponsiveness to ACh was recorded at 18 24 hr. A marked accumulation of eosinophils in the peribronchial regions was observed on histological preparations of lung specimens collected 4 hr or 24 hrafler ovalbumin exposure. Pretreatment of the guinea-pigs by BN 50730 or BN 52021 did not modify the eosinophil accumulation in the peribronchial area. No significant difference in the number of eosinophils collected in the bronchoalveolar lavage fluid is observed, 24 hr posl-ovalbumin challenge, under the pretreatment with BN 52021 or BN 50730. Pretrealment of guinea-pigs by BN 50730 or BN 52021 significantly reduced the PAF-induced (100μg/ml) increase in eosinophil number in the peribronchial area. By contrast, they did not inhibit the eosinophilia induced by aerosol administration of LTB4 (5 μg/ml). These results suggest that the bronchial hyperresponsiveness observed in this study is associated with eosinophil accumulation in the lung. The potent inhibition of the bronchial hyperresponsiveness by the two unrelated antagonists of PAF suggests that the lipid mediator is involved in its triggering and duration, but not in the eosinophil infiltration.