The small chemical
vacuolin-1 induces rapid formation of large vacuoles in various cell types. In epithelial cells,
vacuolin-1 has been shown to inhibit Ca2+
ionophore-induced exocytosis depending on experimental conditions used but had no effect on repair of damaged membranes. However, it is not known whether
vacuolin-1 could inhibit exocytosis induced by immunoreceptor triggering in professional secretory cells and whether there is any correlation between effect of
vacuolin-1 on exocytosis and membrane repair in such cells. Here we show that in rat basophilic
leukemia (RBL-2H3) cells activated by the high-affinity
IgE receptor (FcepsilonRI) triggering
vacuolin-1 enhanced exocytosis. Under identical conditions of activation,
vacuolin-1 inhibited exocytosis in mouse bone marrow-derived mast cells (BMMCs). This inhibition was not reflected by decreased phosphorylation of the FcepsilonRI alpha and beta subunits, linker for activation of T cells, non-T cell activation linker, Akt and
MAP kinase Erk, and uptake of extracellular Ca2+, indicating that early activation events are not affected. In both cell types
vacuolin-1 led to formation of numerous vacuoles, a process which was inhibited by
bafilomycin A1, an inhibitor of
vacuolar H+-ATPase.
Thapsigargin- or Ca2+
ionophore A23187-induced exocytosis also showed different sensitivity to the inhibitory effect of
vacuolin-1. Pretreatment of the cells with
vacuolin-1 followed by permeabilization with
bacterial toxin streptolysin O enhanced Ca2+-dependent repair of plasma membrane lesions in RBL-2H3 cells but inhibited it in BMMCs. Our data indicate that lysosomal exocytosis exhibits different sensitivity to
vacuolin-1 depending on the cell type analyzed and mode of activation. Furthermore, our results support the concept that lysosomal exocytosis is involved in the repair of injured plasma membranes.