Effect of azelastine on platelet-activating factor-induced microvascular leakage in rat airways

To determine the effect of the antiallergic drug azelastine on airway mucos al inflammation, we studied airway microvascular permeability in response t o platelet-activating factor (PAF) in pathogen-free rats. Vascular permeabi lity and neutrophil accumulation were assessed by the percent area occupied by Monastral blue-labeled blood vessels and by myeloperoxidase-containing granulocytes, respectively, in whole mounts of the trachea and main bronchu s. Intravenous PAF caused dose-dependent increases in the area density of M onastral blue-labeled vessels and neutrophil influx, and the former effect was inhibited by depletion of circulating neutrophils by cyclophosphamide o r treatment with the neutrophil elastase inhibitor ONO-5046. Pretreatment w ith azelastine inhibited PAF-induced vascular leakage without affecting neu trophil accumulation. This inhibitory effect of azelastine was not seen in neutropenic rats and ONO-5046-treated rats. PAF increased neutrophil elasta se contents in bronchoalveolar lavage fluid, an effect that was inhibited b y azelastine. Therefore, azelastine attenuates PAF-induced airway mucosal m icrovascular leakage, probably involving inhibition of the release of neutr ophil elastase from activated neutrophils.