Oxidative Response of Phagocytes to Parasite Invasion

Abstract

Phagocytes destroy intracellular pathogens and extracellular targets in part by the production of toxic oxygen metabolites--namely, superoxide, hydrogen peroxide, hydroxyl radicals and possibly singlet molecular oxygen. The toxicity of hydrogen peroxide is increased greatly by peroxidase and a halide. A peroxidase that can be used for this purpose is present in neutrophils and monocytes (myeloperoxidase), but is lost when the monocyte matures into a macrophage; a different peroxidase is present in eosinophils. The latter enzyme, because of its strong positive charge, binds to the surface of parasites; any phagocyte in the region, when appropriately stimulated, may provide the hydrogen peroxide required for completion of the peroxidase system. Further, peroxidase-coated organisms are more readily killed when ingested by macrophages than are uncoated organisms. Oxygen-dependent toxicity requires the production of toxic oxygen products by phagocytes in amounts sufficient to overcome the protective capacity of endogenous scavengers in the parasite. The latter include catalase and glutathione peroxidase, which degrade hydrogen peroxide, and superoxide dismutase which dissipates superoxide. The host defence against parasites appears to depend in part on this balance between toxic oxygen metabolites and scavengers.