Oxidants from human neutrophil

Schmidt, H. H. H. W., Seifert, R., Bohme, E. (1989). Formation and release of nitric oxide from human neutrophils and HL-60 cells induced by a chemotactic peptide, platelet activating factor and leukotriene B4. FEBS Lett. 244, 357-60. 

T4. Tauber, A. 1., Gabig, T. G., and Babior, B. M., Evidence for production of oxidizing radicals by the particulate Oi-forming system from human neutrophils. Blood 53, 666-676 (1979). 

Numerous studies have demonstrated that degradation products of (3-carotene exhibit deleterious effects in cellular systems (Alija et al., 2004, 2006 Hurst et al., 2005 Salerno et al., 2005 Siems et al., 2003). A mixture of (3-carotene degradation products exerts pro-apoptotic effects and cytotoxicity to human neutrophils (Salerno et al., 2005 Siems et al., 2003), and enhances the geno-toxic effects of oxidative stress in primary rat hepatocytes (Alija et al., 2004, 2006), as well as dramatically reduces mitochondrial activity in a human leukaemic cell line, K562, and RPE 28 SV4 cell line derived from stably transformed fetal human retinal pigmented epithelial cells (Hurst et al., 2005). As a result of degradation or enzymatic cleavage of (3-carotene, retinoids are formed, which are powerful modulators of cell proliferation, differentiation, and apoptosis (Blomhoff and Blomhoff, 2006). 

At the same time the interaction of superoxide with MPO may affect a total superoxide production by phagocytes. Thus, the superoxide adduct of MPO (Compound III) is probably quantitatively formed in PMA-stimulated human neutrophils [223]. Edwards and Swan [224] proposed that superoxide production regulate the respiratory burst of stimulated human neutrophils. It has also been suggested that the interaction of superoxide with HRP, MPO, and LPO resulted in the formation of Compound III by a two-step reaction [225]. Superoxide is able to react relatively rapidly with peroxidases and their catalytic intermediates. For example, the rate constant for reaction of superoxide with Fe(III)MPO is equal to 1.1-2.1 x 1061 mol 1 s 1 [226], and the rate constants for the reactions of Oi and HOO with HRP Compound I are equal to 1.6 x 106 and 2.2 x 1081 mol-1 s-1, respectively [227]. Thus, peroxidases may change their functions, from acting as prooxidant enzymes and the catalysts of free radical processes, and acquire antioxidant catalase properties as shown for HRP [228] and MPO [229]. In this case catalase activity depends on the two-electron oxidation of hydrogen peroxide by Compound I. 

BW-755C and its congeners can be considered as reducing agents either because they are dihydroaromatic compounds, or because of the presence of a hydrazine moiety, which is easily oxidized. In the latter vein, the amid-razone CBS-1114 (100) inhibited platelet CO and 12-LO, the release of 5-LO products from human or rabbit neutrophils (1-10 /M), and leukocyte... 

Many inhibitors of catabolic pathways cause a decrease in cellular heat dissipation. They are therefore valuable tools to indicate the sources of the dissipation and give clues to the relative importance of each pathway in overall metabolic activity (see reviews by Kemp, 1987, 1993 Monti, 1987, 1991). To give a few examples from these reviews, sodium fluoride is a classical inhibitor of glycolysis and it has been shown to substantially reduce heat dissipation by human erythrocytes, lymphocytes, neutrophils, and murine macrophages, indicating the contribution of this pathway to metabolic activity. Cyanide inhibits oxidative phosphorylation by mitochondria at the cytochrome c oxidase complex (site 3) and studies revealed that it decreased heat production in a mouse LS-L929 fibroblast cell line but had no effect on human erythrocytes and neutrophils and murine macrophages, all of which lack mitochondria. Sodium azide inhibits at the same site and so it should come as no surprise that it had no effect on human neutrophils and lymphocytes, but it did reduce heat production by lymphocyte hybridoma cells, which contain... 

Whatever the actual reagents might be, it has been shown that O2 can oxidize sulfite and initiate a free-radical chain reaction, or oxidize iron-containing clusters present in enzymes, such as aconitase and fumarases, freeing Fe(II), which in turn initiates a Fenton-like chemistry hy interacting with hydrogen peroxide (317). Fe(II) release from transferrin has also been observed following O2 secretion by stimulated human neutrophils (318). 

Schmitz FJ, Veldkamp KE, Van Kcssel KP et aL Delta-toxin from Staphylococcus aureus as a costimulator of human neutrophil oxidative burst. J Infect Dis 1997 176 1531-1537. 

Elbim, C., Prevot, M. H., Bouscarat, F., Franzini, E., Chollet-Martin, S., Hakim, J., and Gougerot-Pocidalo, M. A. (1994) Polymorphonuclear neutrophils from human immunodeficiency virus-infected patients show enhanced activation, diminished fMLP-induced L-selectin shedding, and an impaired oxidative burst after cytokine priming. Blood 84,2759-2766. 

Activation of human neutrophils with opsonized particles in the presence of a nontoxic dose of 1-naphthol resulted in inhibition of superoxide anion production but not of the phagocytic activity of the cells ( T Hart et al. 1990). The inhibition is not at the level of cellular activation since the N-formyl-met-leu-phe-induced rise of intracellular free calcium was unaffected. The (metabolic) activation of 1-naphthol to 1,4-naphthoquinone by reaction with H2O2 from the oxidative burst is a necessary event for the inhibition to occur. 

Joffe A, Geacintov NE, Shafirovich V (2003) DNA lesions derived from the site selective oxidation of guanine by carbonate radical anions. Chem Res Toxicol 16 1528 1538 Masuda M, Suzuki T, Friensen MD, Ravanat JL, Cadet J, Pignattelli B, Nishino H, Ohshi-ma H (2001) Chlorination of guanosine and other nucleosides by hypochlorous acid and myeloperoxidase of activated human neutrophils catalysis by nicotine and trimethylamine. J Biol Chem 276 40486 10496... 

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