Possible Role of Arachidonic Acid and Its Metabolites in Mediator Release from Rat Mast Cells

Abstract

Abstract The role of arachidonic acid (AA) metabolism in the release of inflammatory mediators from rat mast cells was studied. Eicosa-5,8,11,14-tetraynoic acid (ETYA), an acetylenic analog of AA, was found to inhibit histamine release induced by anti-IgE, concanavalin A (Con A), or the ionophore A-23187 with ID50 values of 65, 50, and 17 µM, respectively. Mediator release was not affected by aspirin or indomethacin in concentrations up to 60 µM. Addition of free AA (0.1 to 100 µM) to unstimulated mast cells did not initiate noncytotoxic mediator release. Preincubation of mast cells with 1 to 10 µM AA inhibited subsequent release induced by anti-IgE or Con A (up to 38%). This inhibition of release was blocked if aspirin (10 µM) or indomethacin (10 µM) was present, suggesting that AA inhibition was mediated by cyclo-oxygenase products. When AA was added after secretion was initiated by anti-IgE or Con A, a modest potentiation of release was noted. These studies suggest that AA metabolism by enzyme systems other than cyclo-oxygenase is an integral part of the mast cell secretory process. Availability of free AA, however, does not appear to be a sufficient condition to initiate secretion by otherwise unstimulated cells. Activation of mast cells by secretory signals appears to lead to altered AA metabolism which in turn appears to be involved in the secretion of inflammatory mediators.