Release of arachidonic acid metabolites and histamine from sensitized guinea-pig lung following antigen challenge.

1. The time course of mediator release and the hypothesis that the ratio of eicosanoids to histamine might alter with the intensity of stimulus or its route of administration has been explored in isolated perfused lung from sensitized guinea-pigs challenged with ovalbumin. 2. Histamine and prostaglandin release was rapid in onset and virtually complete within 10 min. Thromboxane B2 (TXB2) and leukotriene D4 (LTD4) release, however, was more sustained. Release of the major prostanoid metabolites was relatively delayed compared to that of the parent compounds and was more sustained. 3. Mediator release was antigen-dose dependent and TXB2, prostaglandin D2 (PGD2) and LTD4 release linearly related to histamine concentrations (P less than 0.05). However, the ratio of the percentage maximum release of eicosanoids relative to histamine was greatest with low doses of ovalbumin. 4. At a low antigen dose (10 micrograms ovalbumin), histamine and prostanoid release was greatest when the challenge was via the airway rather than into the pulmonary artery and the greatest differences were in PGF2 alpha levels. At near maximal challenge (1 mg ovalbumin) there was little difference in concentrations of PGD2, TXB2, 6-oxo-PGF1 alpha and LTD4 by either route, but PGF2 alpha levels remained greater. 5. The results indicate that biologically active amounts of prostanoids may be released from sensitized lung at low degrees of mast cell activation and that differences in mediator release following antigen administration to the airway or into the pulmonary vasculature simply reflects its accessibility to sensitized cells.