Gangliosides enhance IgE receptor-dependent histamine and LTC4 release from human mast cells

Releasability of mast cells and basophils to an IgE-dependent stimulus is regulated by extra- and intracellular factors which are only partly understood. As gangliosides are known to modulate receptor-dependent processes in various cell types, we have evaluated the effect of these molecules on mast cell mediator release. Human skin mast cells and the human mast cell line HMC1 were pretreated with the gangliosides GM2, GM3 and GD1a as well as with asialo-GM3, heparin and buffer alone (controls). After washing, the cells were stimulated with anti-IgE, calcium ionophore A 23187, N-FMLP or substance P. All gangliosides but not asialo-GM3 and heparin augmented anti-IgE-induced mediator release in a dose-dependent fashion, whereas the release to A 23187, N-FMLP and substance P remained unaffected. Only sequential but not simultaneous addition of ganglioside and anti-IgE showed an enhancement in mediator release compared to controls. Mediator release in both ganglioside-pretreated cells and controls was calcium-dependent and could be inhibited by pretreatment of cells with staurosporine or dibutyryl cAMP, indicating an unchanged signal transduction. Gangliosides appear to specifically optimize IgE-receptor-ligand interaction and alterations in cellular gangliosides could thus induce enhanced releasability as observed in atopics.