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  • Title: Platelet-activating factor stimulates secretion of respiratory glycoconjugate from human airways in culture.
    Author: Goswami SK, Ohashi M, Stathas P, Marom ZM.
    Journal: J Allergy Clin Immunol; 1989 Nov; 84(5 Pt 1):726-34. PubMed ID: 2478607.
    Abstract:
    Platelet-activating factor (PAF) is a naturally occurring phospholipid that acts as a potent mediator of inflammation and bronchoconstriction. Since mucus secretion accompanies many pulmonary-allergic reactions, we examined the effect of PAF on respiratory glycoconjugate (RGC) release from human airways in vitro. PAF, in concentrations of 5 to 100 ng/ml, induced a specific, dose-dependent release of [3H]RGC from human airways in vitro (range of 15% to 120% increase above control, p less than 0.001; n = 8). Time-course studies revealed that RGC release reached its peak level by 60 minutes, and by the end of 4 hours, decreased almost to the baseline level, suggesting a stimulatory effect on secretion rather than synthesis. PAF analog, RO 19-3704, which is a PAF-receptor antagonist, inhibited RGC secretion mediated by PAF in a dose-dependent manner with an inhibitory concentration of 50% of 70 ng/ml. BW 755C and nordihydroguaiaretic acid, but not indomethacin, inhibited RGC release by PAF. LY 171883, a specific leukotriene D4-receptor antagonist, totally inhibited the release of RGC by PAF. Similar results were observed with FPL 55712. PAF-treated airways generated peptidoleukotrienes significantly above control airways in association with enhanced RGC secretion. This enhanced effect on RGC secretion was specifically and significantly blocked by LY 171883. Atropine (10(-5) mol/L) augmented the secretagogue activity of PAF, whereas dexamethasone (10(-5) mol/L) inhibited it. These data indicate that PAF is a significant RGC secretagogue that affects the RGC-secreting cells via the lipoxygenase pathway of arachidonic acid metabolism and the generation of leukotrienes in the airways, but not through the cholinergic receptors on the secretory cells.
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