Bronchoconstriction induced by platelet-activating factor in the guinea pig and its inhibition by CV-3988, a PAF antagonist: serial changes in findings of lung histology and bronchoalveolar lavage cell population.

Abstract

Platelet-activating factor (PAF), 1-o-alkyl-2-acetyl-sn-glyceryl-3-phosphoryl choline, induced acute bronchoconstriction in the guinea pig when intravenously administered in a very small dosage (30 ng/kg). Serial changes in findings of lung histology and bronchoalveolar lavage (BAL) cell population were studied. Severe bronchial smooth muscle contraction and hypersecretion were followed by eosinophil infiltration. Increase in the number of eosinophils was also elucidated by BAL. Prominent damage to the ciliated bronchial epithelial cells was suggested from the lung histology, which was also supported by the fact that a number of ciliated cells was recovered by BAL. Late-onset bronchial constriction after PAF infusion was not observed. CV-3988, one of the specific PAF antagonists, completely inhibited the PAF-induced bronchoconstriction when administered before the PAF infusion. We concluded that PAF is a potent in vivo agent which brings about hypersecretion, eosinophil accumulation, bronchial epithelial damage as well as bronchoconstriction in the guinea pig, and that its action is completely blocked by CV-3988.