Macrophage Activation: Enhanced Oxidative and Antiprotozoal Activity

Abstract

Although only one of the array of secretory properties displayed by activated macrophages, the capacity to generate increased amounts of reactive oxygen intermediates is a consistent biochemical marker of activation with clearly relevant biologic effects (Nathan et al., 1980). Thus, the ability to secrete high levels of superoxide anion (O₂ ⁻) and hydrogen peroxide (H₂O₂) appears to contribute in an important way to the capacity to exert enhanced antimicrobial activity—a particularly key expression of the activated state (North, 1979). Current evidence suggests, for example, that (1) those mononuclear phagocytes that are capable of killing intracellular pathogens such as protozoa, fungi, and mycobacteria depend in large measure on this oxygen-dependent mechanism (Haidaris and Bonventre, 1982; Murray et al., 1979; Murray and Cohn, 1980; Murray, 1981a, 1982b; Nathan et al., 1979; Sasada and Johnston, 1980; Walker and Lowrie, 1981), and (2) secreted O₂ ⁻ and H₂O₂ may also be active against certain extracellular microbial targets too large to be ingested (Diamond et al., 1982; Kazura et al., 1981).