Effect of long-term administration of platelet-activating factor on pulmonary responsiveness and morphology in the guinea pig.

To further substantiate the possible role of platelet-activating factor (PAF) in the development of bronchial hyperreactivity, Alzet osmotic minipumps loaded with the autacoid or solvent alone were placed under the back skin of male Hartley guinea pigs and connected to the jugular vein for 15 days. As compared to the animals treated with solvent alone, guinea pigs receiving PAF (20 micrograms/kg/h, 15 days) exhibited a hyperresponsiveness to histamine that was not observed in those simultaneously treated with PAF and the PAF antagonist BN 52021. Lungs from PAF-treated animals were congestive in appearance, bronchi and bronchioli were contracted, Reisseisen muscles were markedly hypertrophied, and a muciparous metaplasia of the endothelium was observed. The number of eosinophils was significantly increased in the parenchyma, as was the number of mast cells in the peribronchial zones in the lungs from guinea pigs chronically treated with PAF. Lungs from control animals did not show morphologic alterations or eosinophil and mast cell infiltration. These data indicate that long-term treatment with PAF induces profound alterations in the respiratory system, resembling those observed in asthmatic patients. This result is in keeping with the possible role of this autacoid in the development of bronchial hyperreactivity.