There is an ongoing debate about the specific mechanisms of the killing of ingested microbes in phagolysosomes. Numerous reports demonstrate the involvement of the myeloperoxidase (MPO)-H2O2-halide system in the killing of microbes. The current view is that in normal neutrophils, HOCl is primarily responsible for oxidative killing. It has been shown that HOCl is a much more potent killer than H2O2 and therefore MPO- H2O2-halide system has generally been considered essential in killing. This is, however, disapproved by the fact that the persons suffering from subtotal or total MPO-deficiency with an estimated prevalence of 1 of 2000-4000 individuals have usually a normal health status. Surprisingly, reviews dealing with the role of MPO in killing ignore macrophages known to contain no MPO but capable of killing microbes.

The findings of Segal’s group challenge the established view about the role of oxidants in direct killing of bacteria. According to their impression, the main role of NADPH oxidase is not superoxide generation but to polarize the phagosomal membrane via electrogenic transmembrane electron transfer thereby driving the influx of potassium ions to increase the ionic strength of the phagosome. Increased osmolarity then causes the solubilization of elastase and cathepsin G from proteoglycan complexes. Presumably these proteases then kill the ingested bacteria.

In this study, we experimentally show that the phagolysosomal concentration of H2O is high enough for killing one bacterial cell without the participation of MPO.