IgE-dependent and ionophore-induced generation of leukotrienes by dog mastocytoma cells.

Isolated dog mastocytoma cells sensitized with dog anti-ragweed IgE and challenged with ragweed antigen generate the C-6 peptide leukotriene (LT) constituents of the slow-reacting substance of anaphylaxis (SRS-A), LTC4 and LTD4, and the potent leukocyte chemotactic factor, LTB4, as well as 15-hydroxyeicosatetraenoic acid (15-HETE), 12-HETE, and 5-HETE. Antigen challenge evoked a mean maximum production of LTC4, LTD4, and LTB4, respectively, of 16.3 ng, 4.6 ng, and 6.7 ng per 10(6) mastocytoma cells within 5 min at 37 degrees C, which was maintained for up to 45 min. The maximum production of leukotrienes by mastocytoma cells activated with optimum concentrations of 0.2 to 1 microM calcium ionophore A23187 was 35% to 50% greater than that achieved by antigen challenge, without alterations in the relative quantities of leukotrienes, but was realized only after 30 min at 37 degrees C. The leukotriene products of mastocytoma cells were identified by high-performance liquid chromatography, spectral properties, and immunoreactivity with mono-specific antisera, and exhibited the same concentration-dependence of biologic activity as authentic synthetic standards. The ratio of quantities of C-6 peptide leukotrienes generated was attributable in part to the rate of peptidolytic conversion of LTC4 to LTD4 in the mastocytoma cells, which was 33% per 30 min at 37 degrees C. The rapid maximum response to IgE-dependent stimulation and the unique spectrum of products distinguishes the secretion of leukotrienes by dog mastocytoma cells from that by basophils and some other types of mast cells and suggests diverse contributions of mast cell leukotrienes to immediate and late hypersensitivity reactions.