Role of PAF in the late airway microvascular leakage induced by antigen in IgE‐sensitized rat

Summary—The effect of the antagonist of platelet‐activating factor (PAF), BN 50730, on PAF‐and antigen‐ induced increase in microvascular leakage, using Evans blue dye as an index of permeability, was investigated in rat pulmonary tissues. PAF (1 μg/kg, iv) induced a marked increase in Evans blue dye content in trachea, main bronchi and small bronchi, that was significantly reduced upon pretreatment of the rats with BN 50730 (25 mg/kg, orally) and by the serotonin antagonist, methysergide (1 mg/kg, iv), only in the small bronchi. Serotonin also induced an increase in microvascular leakage in the three tissues that was significantly inhibited when the animals were treated with methysergide but not by BN 50730. In contrast, histamine and lyso‐PAF did not induce significant increase in Evans blue dye content. Intravenous injection of antigen to IgE‐sensitized rats induced a biphasic increase in vascular permeability. 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 treatment of the rats with methysergide, whereas, BN 50730 was ineffective. A late increase in vascular permeability was noted in the three tissues, with a maximum at 120 minutes and representing 30–40% of the magnitude of the first phase. Administration of BN 50730 (25 mg/kg) to the animals, evoked a significant inhibition of this increase in microvascular 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 trachea, 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 the marked inhibition of this process by the selective PAF antagonist BN 50730.