Neutrophil oxidase

Woodman, R.C. et al., Prolonged recombinant interferon-gamma therapy in chronic granulomatous disease Evidence against enhanced neutrophil oxidase activity, Blood, 79, 1558, 1992. 

Volpp, B. D., Nauseef, W. M., Clark, R. A. (1988). Two cytosolic neutrophil oxidase components absent in autosomal chronic granulomatous disease. Science 242,... 

Al-Mohanna FA, Ohishi I, Hallett MB (1987) Botulinum C2 toxin potentiates activation of the neutrophil oxidase. Further evidence of a role for actin polymerization. In FEES Letters. 219 40-4... 

Superoxide is formed (reaction 1) in the red blood cell by the auto-oxidation of hemoglobin to methemo-globin (approximately 3% of hemoglobin in human red blood cells has been calculated to auto-oxidize per day) in other tissues, it is formed by the action of enzymes such as cytochrome P450 reductase and xanthine oxidase. When stimulated by contact with bacteria, neutrophils exhibit a respiratory burst (see below) and produce superoxide in a reaction catalyzed by NADPH oxidase (reaction 2). Superoxide spontaneously dismu-tates to form H2O2 and O2 however, the rate of this same reaction is speeded up tremendously by the action of the enzyme superoxide dismutase (reaction 3). Hydrogen peroxide is subject to a number of fates. The enzyme catalase, present in many types of cells, converts... 

Clancy, R.M., Leszczynska-Piziak, J. and Abramason, S.B. (1992). Nitric oxide inhibits neutrophil superoxide anion production via a direct action on the NADPH oxidase. J. Clin. Invest. 90, 1116-1121. 

Watson, F., Robinson, J. and Edwards, S.W. (1991). Protein kinase c-dependent and independent activation of the NADPH-oxidase of human neutrophils. J. Biol. Chem. 266, 7432-7439. 

Grisham, M.B., Hernandez, L.A. and Granger, D.N. (1986). Xanthine oxidase and neutrophil infiltration in intestinal ischaemia. Am. J. Physiol. 251, G567-G574. 

Kvietys, P.R, Twohig, B., Danzell, J. and Specian, RD. (1990). Ethanol-induced injury to the rat gastric mucosa. Role of neutrophil and xanthine oxidase-derived radicals. Gastroenterology 98, 909-920. 

Phon, S.H., Gannon, D.E., Varan, J., Ryan, V.S. and Ward, P.A. (1989). Xanthine oxidase activity in rat pulmonary artery endothelial cells and its alteration by activated neutrophils. Am. J. Path. 134, 1201-1211. 

Thomas, P.D., Mao, G.D., Rabinovitch, A. and Posnansky, M.J. (1993). Inhibition of superoxide generating NADPH oxidase of human neutrophils by lazaroids. Biochem. Pharmacol. 45, 241-251. 

Inflammatory cell phenomenon are also contributors to lipid peroxidation. Activated neutrophils may adhere to damaged endothelium and amplify traumatic, ischaemic or ischaemia-reperfiision injury. Many cyclooxygenase products of the metabolism of atachidonic acid modulate the inflammatory responses of cells. Macrophages, neutrophils and microglia are important sources of reactive oxygen at the injury site. When activated, they produce a respiratory burst that is traced to activated nicotinamide adenine dinucleotide (NADPH/NADH) oxidase. 

Figure 10.2 Possible sites for NADPH-oxidase assembly and activity in human neutrophils. Reprinted from Dahlgren and Karlsson, 1999. Copyright (1999), with permission from Elsevier Science.

Historically, leukocyte NADPH oxidase was the first discovered enzyme of this type the existence of this enzyme in neutrophils was reported in 1962-1966 [59-61]. (As the evidence of superoxide production in biological systems has been obtained several years later, at that time the nature of oxygen species produced by leukocytes was of course unknown.) And only about 10 years later, Babior et al. [62] have shown that the activation of human neutrophils resulted in the production of superoxide. The structure of leukocyte NADPH has been widely discussed and well-established [57]. Superoxide production catalyzed by NADPH oxidase is described by Reaction (5) ... 

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]. 

It follows from the above that the neutrophil-mediated LDL oxidation may occur by both NADPH oxidase- and MPO-dependent mechanisms. It was recently demonstrated [162] that the rates of formation of phosphatidylcholine and cholesteryl ester hydroperoxides during LDL oxidation by PMA-stimulated neutrophils of MPO-knockout mice were about 66% and 44% of those by wild-type neutrophils. In both cases LDL oxidation was inhibited by SOD. These findings suggest that superoxide mediates both NADPH oxidase- and MPO-dependent pathways of oxidation by stimulated neutrophils. 

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