Which of the following helps in generating reactive oxygen intermediate in the neutrophil
Ref Robbins 9/e p79 Killing and Degradation of Phagocytosed Microbes. The culmination of the phagocytosis of microbes is killing and degradation of the ingested paicles. The key steps in this reaction are the production of microbicidal substances within lysosomes and fusion of the lysosomes with phago- somes, thus exposing the ingested paicles to the destruc- tive mechanisms of the leukocytes (Fig. 2-8). The most impoant microbicidal substances are reactive oxygen species (ROS) and lysosomal enzymes. The production of ROS involves the following steps: * Phagocytosis and the engagement of various cellular receptors stimulate an oxidative burst, also called the respiratory burst, which is characterized by a rapid increase in oxygen consumption, glycogen catabolism (glycogenolysis), increased glucose oxidation, and production of ROS. The generation of the oxygen metabolites is due to rapid activation of a leukocyte NADPH oxidase, called the phagocyte oxidase, which oxi- dizes NADPH (reduced nicotinamide adenine dinucleo- tide phosphate) and, in the process, conves oxygen to superoxide ion (O2 * ) (see Fig. 1-18, B, Chapter 1). * Superoxide is then conveed by spontaneous dismuta- tion into hydrogen peroxide (O2 * + 2H+ - H2O2). These ROS act as free radicals and destroy microbes by mecha- nisms that were described in Chapter 1. * The quantities of H2O2 produced generally are insuffi- cient to kill most bacteria (although superoxide and hydroxyl radical formation may be sufficient to do so). However, the lysosomes of neutrophils (called azuro- philic granules) contain the enzyme myeloperoxidase (MPO), and in the presence of a halide such as Cl- , MPO conves H2O2 to HOCl* (hypochlorous radical). HOCl* is a powerful oxidant and antimicrobial agent (NaOCl is the active ingredient in chlorine bleach) that kills bacteria by halogenation, or by protein and lipid peroxidation. Founately, the phagocyte oxidase is active only after its cytosolic subunit translocates to the membrane of the pha- golysosome; thus, the reactive end products are generated mainly within the vesicles, and the phagocyte itself is not damaged. H2O2 is eventually broken down to water and O2 by the actions of catalase, and the other ROS also are degraded (Chapter 1). Reactive nitrogen species, paicu- larly nitric oxide (NO), act in the same way as that described for ROS.
NADPH oxidase
SOD (superoxide dismutase)
Catalase
Glutathione peroxidase
General anatomy