The role of the respiratory burst of phagocytes in host defense.
Generation of reactive oxygen species is a critical event in successful host defense against invading organisms. Work spanning at least 25 years has demonstrated that both neutrophils and macrophages rely on a variety of oxidants to damage bacterial constitutents. The neutrophil is armed with two different oxygen-dependent defenses, while the macrophage relies solely on nonenzymatic oxidant generation. The primary granules of neutrophils contain the enzyme myeloperoxidase, which combines with H2O2 and ultimately leads to production of many toxic oxidant species: Halogens, hypochlorous acid, chloramines, aldehydes, and singlet oxygen. All of these molecules are involved in potentially toxic structural alterations in the pathogen. MPO-independent oxidant generation in neutrophils and macrophages involves the generation of highly toxic species derived from the interaction of O2- and H2O2, such as hydroxyl radical and singlet oxygen. Recent work has concentrated on determining how the interaction of a phagocyte with a foreign particle ultimately triggers the oxidant cascade. Exciting work in the past several years has focused on the proposal that protein kinase C and intracellular Ca2+ are two important focal points, and the activation of these two species leads to NADPH oxidase activation and subsequent conversion of O2 to O2-. The exact mechanism coupling stimulus binding to response promises to be an exciting area of research in the years to come.
Shepherd
V L
VL
Department of Medicine, University of Tennessee, Memphis 38163.
D006801:Humans; D008168:Lung / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D010101:Oxygen Consumption; D010427:Pentose Phosphate Pathway; D010586:Phagocytes / Q000276:immunology* / Q000378:metabolism; D010587:Phagocytosis; D012141:Respiratory Tract Infections / Q000276:immunology; D013481:Superoxides / Q000378:metabolism
D013481:Superoxides