Antigen-induced sulfidopeptide leukotriene release from the guinea pig superfused trachea

The effect of antigen (ovalbumin) challenge on smooth muscle contraction and release of sulfidopeptide leukotrienes and histamine from superfused, actively sensitized guinea pig trachea was examined. Maximum concentrations of ovalbumin caused the release of 16 +/- 4 ng/g immunoreactive sulfidopeptide leukotriene (i-LT) and 27 +/- 3% of the endogenous histamine (x +/- S.E.M., n = 19). High performance liquid chromatography combined with a sulfidopeptide leukotriene radioimmunoassay was used to demonstrate that on a molar basis, approximately 10% of the leukotriene immunoreactivity recovered was LTC4, 45% LTD4 and 45% LTE4. Indomethacin slightly increased ovalbumin-induced histamine release and substantially enhanced (3-fold) i-LT release from the trachea. Neither the profile nor rate of sulfidopeptide leukotriene release was altered by indomethacin. Indomethacin had no effect on the maximum amplitude of the antigen-induced contraction but significantly enhanced the magnitude of contraction observed after 10 min of antigen exposure. These results demonstrate that actively sensitized airways synthesize and release sulfidopeptide leukotrienes upon challenge with specific antigen and that endogenously formed LTC4 is efficiently metabolized to LTD4 and LTE4. The results with indomethacin support the hypothesis that indomethacin potentiates antigen-induced airway contraction in vitro by enhancing the release of mast cell associated mediators.