ROLE OF PAF IN THE LATE AIRWAY MICROVASCULAR LEAKAGE INDUCED BY ANTIGEN IN IGE-SENSITIZED RAT

The effect of the antagonist of platelet-activating factor (PAE), BN 5 0730, on PAF-and antigen- induced increase in microvascular leakage, u sing Evans blue dye as an index of permeability, was investigated in r at pulmonary tissues. PAF(1 mu g/kg, iv) induced a marked increase in Evans blue dye content in trachea, main bronchi and small bronchi, tha t was significantly reduced upon pretreatment of the rats with BN 5073 0 (25 mg/kg, orally) and by the serotonin antagonist, methysergide (1 mg/kg, iv), only in the small bronchi. Serotonin also induced an incre ase in microvascular leakage in the three tissues that was significant ly inhibited when the animals were treated with methysergide but not b y BN 50730. In contrast, histamine and lyso-PAF did not induce signifi cant increase in Evans blue dye content. Intravenous injection of anti gen to IgE-sensitized rats induced a biphasic increase in vascular per meability. An early increase in vascular permeability in trachea, main bronchi and small bronchi was observed 10 minutes after the injection of the antigen, and this phenomenon was significantly reduced upon tr eatment of the rats with methysergide, whereas, BN 50730 was ineffecti ve. A late increase in vascular permeability was noted in the three ti ssues, with a maximum at 120 minutes and representing 30-40% of the ma gnitude of the first phase. Administration of BN 50730 (25 mg/kg) to t he animals, evoked a significant inhibition of this increase in microv ascular leakage, whereas, methysergide only significantly reduced the one induced by antigen in the trachea. These results demonstrate that the early (10 min) antigen-induced microvascular leakage of the trache a, main bronchi and small bronchi in IgE-sensitized rats is primarily due to the release of serotonin. However, the late increase (120 min) in vascular permeability involves PAF generation, as demonstrated by t he marked inhibition of this process by the selective PAF antagonist B N 50730.