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 partl y understood. As gangliosides are known to modulate receptor-dependent processes in various cell types, we have evaluated the effect of thes e molecules on mast cell mediator release. Human skin mast cells and t he human mast cell line HMC1 were pretreated with the gangliosides GM2 , GM3 and GD1a as well as with asialo-GM3, heparin and buffer alone (c ontrols). After washing, the cells were stimulated with anti-IgE, calc ium 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-pr etreated cells and controls was calcium-dependent and could be inhibit ed by pretreatment of cells with staurosporine or dibutyryl cAMP, indi cating an unchanged signal transduction. Gangliosides appear to specif ically optimize IgE-receptor-ligand interaction and alterations in cel lular gangliosides could thus induce enhanced releasability as observe d in atopics.