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Vacuolin-1-modulated exocytosis and cell resealing in mast cells.

Abstract
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.
AuthorsGouse M Shaik, Lubica Dráberová, Petr Heneberg, Petr Dráber
JournalCellular signalling (Cell Signal) Vol. 21 Issue 8 Pg. 1337-45 (Aug 2009) ISSN: 1873-3913 [Electronic] England
PMID19376224 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Heterocyclic Compounds, 4 or More Rings
  • Receptors, IgE
  • vacuolin-1
  • Calcium
Topics
  • Animals
  • Calcium (metabolism)
  • Cell Line, Tumor
  • Cell Membrane (physiology)
  • Exocytosis (drug effects)
  • Heterocyclic Compounds, 4 or More Rings (pharmacology)
  • Mast Cells (drug effects, immunology, metabolism)
  • Mice
  • Phosphorylation
  • Rats
  • Receptors, IgE (immunology, metabolism)
  • Vacuoles (physiology)

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