THE STAPHYLOCOCCAL PORE-FORMING LEUKOTOXINS OPEN CA2+ CHANNELS IN THEMEMBRANE OF HUMAN POLYMORPHONUCLEAR NEUTROPHILS

The ability of leukotoxins secreted by Staphylococcus aureus to modify the permeability of the membrane of human polymorphonuclear neutrophi ls has been studied by spectrofluorometry and appropriate fluorescent probes. This family of bicomponent leukotoxins is constituted by, at l east, three pairs of proteins: LukS-PV/LukF-PV, HlgA/HlgB, HlgC/HlgB. After binding of both components to the membrane, each pair induces in fluxes of divalent cations and ethidium in polymorphonuclear neutrophi ls, although with different intensities. The influx of divalent cation s appears sooner than the influx of ethidium. The pathway for divalent cations is not permeable to monovalent cations (Na+, K+, ethidium(+)) and is blocked by Ca2+ channel inhibitors that do not block the fluxe s of ethidium and monovalent cations. It is concluded that the leukoto xins bind to a receptor linked to a divalent cation-selective channel or to the channel itself which is activated. Then, the leukotoxins ope n a second pathway by insertion into the membrane and subsequent forma tion of aspecific pores allowing an influx of ethidium.