Abstract
Staphylococcal bi-component leukotoxins known as *pore-forming toxins* induce upon a specific binding to membrane receptors, two independent cellular events in human neutrophils. First, they provoke the opening of pre-existing specific ionic channels including Ca2+ channels. Then, they form membrane pores specific to monovalent cations leading to immune cells death. Among these leukotoxins, HlgC/HlgB and HlgA/HlgB γ-hemolysins do act in synergy to induce the opening of different types of Ca2+ channels in the absence as in the presence of extracellular Ca2+. Here, we investigate the mechanism underlying the modulation of Ca2+-independent Ca2+ channels in response to both active leukotoxins in human neutrophils. In the absence of extracellular Ca2+, the Mn2+ has been used as a Ca2+ surrogate to determine the activity of Ca2+-independent Ca2+ channels. Our findings provide new insights about different mechanisms involved in the staphylococcal γ-hemolysins activity to regulate three different types of Ca2+-independent Ca2+ channels. We conclude that (i) HlgC/HlgB stimulates the opening of La3+-sensitive Ca2+ channels, through a cholera toxin-sensitive G protein, (ii) HlgA/HlgB stimulates the opening of Ca2+ channels not sensitive to La3+, through a G protein-independent process, and (iii) unlike HlgA/HlgB, HlgC/HlgB toxins prevent the opening of a new type of Ca2+ channels by phosphorylation/de-phosphorylation-dependent mechanisms.
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