Control of the Oxidative Burst of Human Neutrophils by Staphylococcal Leukotoxins

Abstract

The ability of staphylococcal two-component leukotoxins to induce an oxidative burst and/or to prime human polymorphonuclear cells (PMNs) was studied by using spectrofluorometry or flow cytometry. At sublytic concentrations, the HlgA-HlgB, HlgA-LukF-PV, LukS-PV-LukF-PV, and HlgC-LukF-PV combinations of leukotoxins, but not the LukS-PV-HlgB and HlgC-HlgB combinations, were able to induce H 2 O 2 production similar to the H 2 O 2 production induced by 1 μM N -formyl-Met-Leu-Phe (fMLP). In addition, when added at sublytic concentrations, all of the leukotoxin combinations primed PMNs for H 2 O 2 production induced by fMLP. Leukotoxin activation was dependent on the presence of Ca 2+ and was inhibited by wortmannin, an inhibitor of phosphatidylinositol 3-kinase, but not by N -methyl- l -arginine, an inhibitor of NO generation, which eliminates the possibility that NO plays a role in the action of leukotoxins. At higher concentrations, all leukotoxins inhibited H 2 O 2 production by PMNs activated by fMLP, phorbol 12-myristate 13-acetate (PMA), or the leukotoxins themselves. This inhibition was not related to the pore formation induced by leukotoxins. Intracellular release of H 2 O 2 induced by fMLP and PMA was not primed by leukotoxins but was inhibited. It seems that leukotoxin inhibition of H 2 O 2 release is independent of pore formation but secondary to an intracellular event, as yet unknown, triggered by leukotoxins.

Part of CIRS Nexus · Curated by Lauren Lowenstein, The Biotoxin Lady