Role of platelet-activating factor in the release of neutrophil and eosinophil chemotactic attractants from cultured guinea-pig tracheal epithelial cells.

Abstract

Platelet-activating factor (PAF) has been implicated in the pathogenesis of allergic disease, particularly bronchial asthma, by recruitment and activation of inflammatory cells. In an effort to further elucidate this function of PAF, guinea-pig tracheal mucosa was cultured in the presence of PAF in vitro, and culture supernatants were injected intradermally into normal guinea-pigs. After 6 h, recruitment of the inflammatory cells in the tissue was evaluated as a marker of chemotactic activity. Neutrophil and eosinophil recruitment increased significantly 1 h after PAF stimulation, the latter more than the former. After fractionation of the culture supernatant using molecular sieve filters, the fraction of 10-30 kDa showed greater chemotactic activity than the fractions of below 10 kDA or greater than 30 kDA. This activity was inhibited in a dose-dependent manner (over about 1-100 mg/ml) by treatment with anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibody. These results suggest that PAF induces the release of chemotactic factors for neutrophils and eosinophils from guinea-pig tracheal epithelial cells, and one of these factors may be GM-CSF.