The respiratory burst of phagocytes.

Abstract

The Respiratory Burst of Phagocytes hen exposed to certain stimuli, phagocytes (neu- trophils, eosinophils, and mononuclear phagocytes) undergo marked changes in the way they handle oxygen (1).Their rates of oxygen uptake increase greatly, sometimes more than 50- fold; they begin to produce large amounts of superoxide (O°-) and hydrogen peroxide (H202); and they start metabolizing large quantities ofglucose by way ofthe hexose monophosphate shunt.Because of the sharp increase in oxygen uptake, this series of changes has come to be known as the "respiratory burst."The "respiration" associated with this burst, however, has nothing to do with energy production; rather, its purpose is to generate powerful microbicidal agents by the partial reduction ofoxygen.The respiratory burst results from the activation of an en- zyme, dormant in resting cells, that catalyzes the one-electron reduction of oxygen to °at the expense of NADPH: 02+ NADPH -0 + NADP+ + HW.Most of this 0O reacts rapidly with itself, dismuting to produce oxygen and H202: 20-+ 2H+ -4 H202 + 02.At the same time, glucose is metabolized through the hexose monophosphate shunt in order to regenerate the NADPH that has been consumed by the 0-forming enzyme and by a glu- tathione-dependent H202-detoxifying system that is found in the cytoplasm of the phagocyte.0-and H202, the immediate products of the respiratory burst, are not used by the phagocytes for microbial killing because H202 is only weakly microbicidal and 0-is completely innoc- uous.These compounds are used instead as starting materials for the production of the true microbicidal oxidants of phagocytes.These microbicidal oxidants fall into two classes: oxidized halogens and oxidizing radicals.The production of the former starts with the myeloperoxidase-catalyzed oxidation of Cl-to hypochlorite by H202 (2): CF-+ H202 -ox OC1-+ H20.myeloperoxidase