Platelet activating factor stimulates secretion of mucin by explants of rodent airways in organ culture

Abstract

Platelet activating factor (PAF; 1-o-alkyl-2-0-acetyl-sn-glycero-3-phosphocholine-3-phosphocholine) a potential mediator of anaphylaxis, stimulates secretion of mucin by explants of trachea from four separate rodent species (guinea pig, rat, rabbit, ferret) in organ culture. Enhanced secretion is not a result of cell damage or release of histamine by cells within the explants (e.g., platelets). It is inhibited by equimolar concentrations of the potent PAF-receptor antagonist, Ro 19-3704. PAF provokes production of immunoreactive peptidyl leukotrienes (ir-LTC4, LTD4, LTE4) within the explants. The stimulatory effect of PAF on mucin secretion is blocked by equimolar concentrations of nordihydroguiaretic acid (NDGA) a "mixed" inhibitor of both cyclo- and lipoxygenase pathways of arachidonic acid metabolism. Leukotrienes are localized within tracheobronchial epithelium by immunohistochemical staining, and physical removal of epithelium from explants inhibits production of leukotrienes in vitro under nonstimulated conditions and after exposure to PAF. In addition, the stimulatory effect of PAF on mucin secretion is not altered by FPL-55712, a receptor antagonist of LTD4. These results are consistent with the hypothesis that PAF stimulates secretion of mucin by activating biosynthesis of lipoxygenase products (e.g., peptidyl leukotrienes) within epithelial cells of the respiratory mucosa.