Platelet activating factor stimulates rapid mucin secretion in rat nasal airways in vivo.

Abstract

Platelet activating factor (PAF; 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is a potent bronchoconstrictor and has been implicated in the epithelial exfoliation, inflammatory cell influx, and mucous hypersecretion associated with airways of asthmatics. PAF stimulates mucous secretion in vitro; however, the in vivo effects of PAF on airway mucous secretion are not well documented. To assess the in vivo effects of PAF on airway mucous-goblet cell secretion, Fischer 344/N rats were intranasally instilled with 50 micrograms of PAF or Lyso-PAF (inactive precursor and metabolite) in 100 microL of saline or saline alone (50 microL/naris). Rats were sacrificed 1 or 6 h after instillation, and the anterior nasal cavity was processed for light microscopy. Tissue sections were stained 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 eosinophils. The numbers of epithelial and inflammatory cells and the amounts of intraepithelial mucosubstances within the nasal respiratory epithelium were determined by morphometry. Compared to saline-instilled controls, intranasal instillation of PAF, but not Lyso-PAF, resulted in a significant decrease in the volume density of intraepithelial mucosubstances 1 and 6 h after instillation. Intranasal instillation of PAF also induced a slight neutrophilic and eosinophilic influx 6 h after instillation and a transient decrease in epithelial cell numeric density 1 h post-exposure. Lyso-PAF had no significant effect on any of the measured parameters. This study demonstrates that PAF is a mucous secretagogue in vivo and can induce acute airway epithelial responses in rats similar to those seen in the airways of asthmatics.