Superoxide: The enigmatic chemical chameleon in neutrophil biology

Abstract

Three decades ago, our free radical research group in Ōtautahi Christchurch asked two rather straightforward questions: "What's so super about superoxide?", and "How do neutrophils use superoxide to kill bacteria?" 1-3 Neither question was particularly novel but they were at the heart of understanding the importance of the superoxide radical anion (O −⋅ 2 ) in oxidative stress and host defense. Naively, we thought that an answer to the first question would also satisfy the second question. We hoped that by probing how neutrophils use superoxide to kill ingested bacteria, we would reveal the toxic nature of superoxide. With these answers in hand, we could explain why the enzyme superoxide dismutase is needed to protect cells from oxidative stress. Our naiveté stretched to thinking that these questions would yield quick answers. But, in reality, the central question remains to this day: How does superoxide generation and removal fit into normal physiology? 4

Inside the phagosome: A bacterial perspective

“…Also, most of the HOCl generated in the phagosome was modelled, and confirmed experimentally, to react with neutrophil proteins 12,14 . It is also possible that the superoxide in concert with myeloperoxidase gives rise to oxidants within the phagosome other than HOCl 15 …”

“…12,14 It is also possible that the superoxide in concert with myeloperoxidase gives rise to oxidants within the phagosome other than HOCl. 15 As might be expected for a system that can generate large amounts of damaging species, the activation and duration of the oxidative burst are tightly regulated. The duration of the burst, which is difficult to monitor in individual phagosomes using bulk measures of oxygen consumption, differs between stimuli and can be regulated by several different factors.…”

Neutrophils and their friends

“…Kettle and colleagues in Christchurch revisit the role of superoxide, the most proximate product of the NADPH oxidase-catalyzed electron transfer to molecular oxygen, in antimicrobial activity and in the overall economy of reactive oxygen species within the phagosome. 11 Although itself not microbicidal, superoxide reacts with myeloperoxidase (MPO) to sustain the generation of the potent microbicide, hypochlorous acid (HOCl). Given the prominent contribution of MPO-catalyzed HOCl production to overall oxidant-dependent antimicrobial action in neutrophils, superoxide is, at least in one respect, super.…”

“…For certain, many of our notions as to the biochemical events that transpire within neutrophil phagosomes need revision, starting with the actions of oxidants generated therein. Kettle and colleagues in Christchurch revisit the role of superoxide, the most proximate product of the NADPH oxidase‐catalyzed electron transfer to molecular oxygen, in antimicrobial activity and in the overall economy of reactive oxygen species within the phagosome 11 . Although itself not microbicidal, superoxide reacts with myeloperoxidase (MPO) to sustain the generation of the potent microbicide, hypochlorous acid (HOCl).…”

Effect of fat ingestion on postprandial oxidative status in healthy young women: a pilot study

“…Leukocytes enzymatically produce reactive oxygen species (ROS) and highly reactive oxygen species (hROS) in the innate immune system. ( 1 , 2 ) As a primary ROS, leukocyte NADPH oxidases generate superoxide radicals (O 2 •− ), a precursor of hydrogen peroxide (H 2 O 2 ). ( 1 , 2 ) Myeloperoxidase (MPO), predominantly present in neutrophil granules, catalyzes the conversion of H 2 O 2 to hypochlorite ions (OCl − ), a type of hROS.…”