Phagocytes, O2 reduction, and hydroxyl radical

Abstract

The formation of O2 reduction products by human neutrophils is critical to their elimination of potential pathogens. Hydroxyl radical is a potent oxidizing agent that may be formed by neutrophils through the iron-catalyzed reaction of superoxide and its dismutation product, hydrogen peroxide. Although indirect evidence has implicated hydroxyl radical in a variety of neutrophil-mediated processes, recent studies have not demonstrated hydroxyl radical formation by neutrophils unless an exogenous iron source and chelator were available, and even then neutrophils appear to limit formation of hydroxyl radical. By consuming hydrogen peroxide, the release of myeloperoxidase limits the magnitude of hydroxyl radical production. Lactoferrin released during neutrophil stimulation binds iron in a form incapable of catalyzing hydroxyl radical generation, thereby limiting both the magnitude and the duration of hydroxyl radical formation. Hydroxyl radical resulting from neutrophil superoxide production is likely to occur either in vitro or in vivo only when the target cell (or microenvironment) provides iron in an oxidation state and form capable of catalyzing the formation of hydroxyl radical and when neutrophil prevention systems are overwhelmed.