Phagocytic oxidase

IFN-y has therapeutic activity in chronic granulomatous disease (CGD).34 In CGD, the mechanism of therapeutic activity by IFN-y appears to be associated with enhanced phagocytic oxidase activity and increased superoxide production by neutrophils. However,... 

Tauber, A. I., Borregaard, N., Simons, E., Wright, J. (1983). Chronic granulomatous disease A syndrome of phagocyte oxidase deficiencies. Medicine 62,286-309. 

Shiloh, M.U., MacMicking, J.D., Nicholson, S., Brause, J.E., Potter, S., Marino, M., Fang, F., Dinauer, M., Nathan, C. Phenotype of mice and macrophages deficient in both phagocyte oxidase and inducible nitric oxide synthase, Immunity 1999, 10, 29-38. 

Flavocytochrome b55S (also called b 245) has the unusually low redox potential of -0.245 V. It exists in phagocytic cells as a heterodimer of membrane-associated subunits p22-phox and gp91 -phox where phox indicates phagocytic oxidase. Tire larger 91-kDa... 

Generation of ROS represents an important mechanism of antibacterial defense. OxPLs inhibit oxidative burst induced by fMLP or phorbol ester in isolated neutrophil granulocytes [61]. Different classes of OxPLs suppressed assembly of phagocyte oxidase the effect was not due to cytotoxicity because cell viability was not changed [61]. The inhibitory action on NADPH oxidase may represent a negative feedback preventing excessive production of ROS and damage to host tissues. 

The Respiratory Burst of Phagocytic Cells Involves NADPH Oxidase Helps Kill Bacteria... 

NADPH oxidase is inactive in resting phagocytic cells and is activated upon contact with various ligands (complement fragment C5a, chemotactic peptides, etc)... 

FIGURE 22.1 Synthesis of phagocytic NADPH oxidase upon activation. 

The existence of nitric oxide synthase (NOS) in phagocytes (see below) provides a different kind of stimulation and the inhibition of NADPH oxidase. It has been found [72] that the low physiological concentrations of peroxynitrite formed from NO and superoxide stimulated superoxide production by PMA-activated human PMNs through the ERK MAPK pathway, while higher peroxynitrite concentrations inhibited it. Moreover, NADPH oxidase was inhibited by lidocaine, a sodium-blocker, in OZ-activated neutrophils through the suppression of p47phox translocation [73]. 

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