PLATELET-ACTIVATING-FACTOR STIMULATES RAPID MUCIN SECRETION IN RAT NASAL AIRWAYS IN-VIVO

Platelet activating factor (PAF; 1-O-alkyl-2-acetyl-sn-glycero-3-phosp hocholine) is a potent bronchoconstrictor and has been implicated in t he epithelial exfoliation, inflammatory cell influx, and mucous hypers ecretion associated with airways of asthmatics. PAF stimulates mucous secretion in vitro; however, the in vivo effects of PAF on airway muco us secretion are not well documented. To assess the in vivo effects of PAF on airway mucous-goblet cell secretion, Fischer 344/N rats were i ntranasally instilled with 50 mug of PAF or Lyso-PAF (inactive precurs or and metabolite) in 100 muL of saline or saline alone (50 muL/naris) . Rats were sacrificed 1 or 6 h after instillation, and the anterior n asal cavity was processed for light microscopy. Tissue sections were s tained with either Alcian blue (pH 2.5)/periodic acid-Schiff sequence to detect acidic and neutral intraepithelial mucosubstances or Luna's reagent for eosinophilic granules to differentiate neutrophils and eos inophils. The numbers of epithelial and inflammatory cells and the amo unts of intraepithelial mucosubstances within the nasal respiratory ep ithelium were determined by morphometry. Compared to saline-instilled controls, intranasal instillation of PAF, but not Lyso-PAF, resulted i n a significant decrease in the volume density of intraepithelial muco substances 1 and 6 h after instillation. Intranasal instillation of PA F also induced a slight neutrophilic and eosinophilic influx 6 h after instillation and a transient decrease in epithelial cell numeric dens ity 1 h post-exposure. Lyso-PAF bad no significant effect on any of th e measured parameters. This study demonstrates that PAF is a mucous se cretagogue in vivo and can induce acute airway epithelial responses in rats similar to those seen in the airways of asthmatics.