Staphylococcus aureus α-toxin activates phospholipases and induces a Ca²⁺ influx in PC12 cells

Staphylococcal α-toxin at subcytotoxic concentrations stimulated phosphatidylinositol turnover and arachidonic acid release in undifferentiated cultures of pheochromocytoma PC12 cells. Stimulation of phospholipase A₂ but not C was dependent on extracellular calcium. Addition of staphylococcal α-toxin to PC12 cells caused a dose-dependent, biphasic increase in intracellular calcium measured by fura-2 fluorescence technique. Elevation of intracellular Ca²⁺ content occured with a time course similar to those observed for stimulation of phospholipase A₂. Alteration of membrane structure and formation of staphylococcal α-toxin pores facilitating an influx of Ca²⁺, represent the probable mechanisms by which phospholipases C and A₂ are activated, respectively. These results suggest a possible involvement of Ca²⁺, phosphoinositides and arachidonic acid metabolites in the pathogenic action of staphylococcus α-toxin and caution against the general usage of this] toxin as a permeabilizing agent to study stimulus-secretion coupling in secretory cells.