The role of 5-lipoxygenase products in the development of airway responsiveness induced by platelet activating factor inhalation in dogs]

To determine whether 5-lipoxygenase products are involved in the development of airway responsiveness and in the infiltration of inflammatory cells into the airway after platelet activating factor (PAF) inhalation, we studied the effect of a selective 5-lipoxygenase inhibitor, AA-861 on PAF-induced airway hyperresponsiveness and on the increase of neutrophil and eosinophil counts in bronchoalveolar lavage fluid (BALF) after PAF inhalation in seven dogs. Airway responsiveness to inhaled methacholine was determined by modified Astograph (7Hz oscillation method). PAF (1000 mu/ml) was delivered as an aerosol, generated from a Devilbiss 646 nebulizer for ten minutes. Airway responsiveness to inhaled methacholine increased significantly 3 hr after PAF inhalation (p less than 0.01). After PAF inhalation, neutrophil and eosinophil counts in BALF increased significantly (p less than 0.01), and the levels of thromboxane (Tx)B2 in BALF also increased (p less than 0.05). Pretreated AA-861 significantly inhibited the increase of airway responsiveness after PAF inhalation (p less than 0.01). The increase of neutrophil and eosinophil counts in BALF after PAF inhalation was also inhibited significantly by pretreated AA-861 (p less than 0.01). The levels of TxB2 in BALF did not change after PAF inhalation following pretreatment with AA-861. These results suggest that 5-lipoxygenase products play important roles in the increase of airway responsiveness and in the infiltration of inflammatory cells into the airway after PAF inhalation in dogs. TxA2 released from inflammatory cells may be involved in the increase of airway responsiveness induced by PAF inhalation.