Hemolysis and iodination of erythrocyte components by a myeloperoxidase- mediated system

Abstract Erythrocytes are hemolyzed by myeloperoxidase, an H2O2-generating system (glucose + glucose oxidase; hypoxanthine + xanthine oxidase) and an oxidizable cofactor (chloride, iodide, thyroxine, triiodothyronine). The combined effect of chloride and either iodide or the thyroid hormones is greater than additive. Myeloperoxidase can be replaced by lactoperoxidase in the iodide-, thyroxine and triiodothyronine- dependent, but not in the chloride-dependent, systems. Hemolysis is is inhibited by the peroxidase inhibitors, azide and cyanide, and by catalase and is stimulated by superoxide dismutase when the xanthine oxidase system is employed as the source of H2O2. Hemolysis by the iodide-dependent system is associated with the iodination of erythrocyte components.

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Hemolysis and iodination of erythrocyte components by a myeloperoxidase- mediated system

Blood ◽

10.1182/blood.v45.5.699.bloodjournal455699 ◽

1975 ◽

Vol 45 (5) ◽

pp. 699-707

Author(s):

SJ Klebanoff ◽

RA Clark

Keyword(s):

Superoxide Dismutase ◽

Thyroid Hormones ◽

Glucose Oxidase ◽

Xanthine Oxidase ◽

Combined Effect ◽

Oxidase System ◽

Generating System

Erythrocytes are hemolyzed by myeloperoxidase, an H2O2-generating system (glucose + glucose oxidase; hypoxanthine + xanthine oxidase) and an oxidizable cofactor (chloride, iodide, thyroxine, triiodothyronine). The combined effect of chloride and either iodide or the thyroid hormones is greater than additive. Myeloperoxidase can be replaced by lactoperoxidase in the iodide-, thyroxine and triiodothyronine- dependent, but not in the chloride-dependent, systems. Hemolysis is is inhibited by the peroxidase inhibitors, azide and cyanide, and by catalase and is stimulated by superoxide dismutase when the xanthine oxidase system is employed as the source of H2O2. Hemolysis by the iodide-dependent system is associated with the iodination of erythrocyte components.

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Bactericidal activity of a superoxide anion-generating system. A model for the polymorphonuclear leukocyte.

Journal of Experimental Medicine ◽

10.1084/jem.149.1.27 ◽

1979 ◽

Vol 149 (1) ◽

pp. 27-39 ◽

Cited By ~ 133

Author(s):

H Rosen ◽

S J Klebanoff

Keyword(s):

Uric Acid ◽

Xanthine Oxidase ◽

Bactericidal Activity ◽

Parent Strain ◽

Carotenoid Pigments ◽

Bacterial Killing ◽

Oxidase System ◽

System A ◽

Presence And Absence ◽

Generating System

The acetaldehyde-xanthine oxidase system in the presence and absence of myeloperoxidase (MPO) and chloride has been employed as a model of the oxygen-dependent antimicrobial systems of the PMN. The unsupplemented xanthine oxidase system was bactericidal at relatively high acetaldehyde concentrations. The bactericidal activity was inhibited by superoxide dismutase (SOD), catalase, the hydroxyl radical (OH.) scavengers, mannitol and benzoate, the singlet oxygen (1O2) quenchers, azide, histidine, and 1,4-diazabicyclo[2,2,2]octane (DABCO) and by the purines, xanthine, hypoxanthine, and uric acid. The latter effect may account for the relatively weak bactericidal activity of the xanthine oxidase system when purines are employed as substrate. A white, carotenoid-negative mutant strain of Sarcina lutea was more susceptible to the acetaldehyde-xanthine oxidase system than was the yellow, carotenoid-positive parent strain. Carotenoid pigments are potent 1O2 quenchers. The xanthine oxidase system catalyzes the conversion of 2,5-diphenylfuran to cis-dibenzoylethylene, a reaction which can occur by a 1O2 mechanism. This conversion is inhibited by SOD, catalase, azide, histidine, DABCO, xanthine, hypoxanthine, and uric acid but is only slightly inhibited by mannitol and benzoate. The addition of MPO and chloride to the acetaldehyde-xanthine oxidase system greatly increases bactericidal activity; the minimal effective acetaldehyde concentration is decreased 100-fold and the rate and extent of bacterial killing is increased. The bactericidal activity of the MPO-supplemented system is inhibited by catalase, benzoate, azide, DABCO, and histidine but not by SOD or mannitol. Thus, the acetaldehyde-xanthine oxidase system which like phagocytosing PMNs generates superoxide (O.2-) and hydrogen peroxide, is bactericidal both in the presence and absence of MPO and chloride. The MPO-supplemented system is considerably more potent; however, when MPO is absent, bactericidal activity is observed which may be mediated by the interaction of H2O2 and O.2- to form OH. and 1O2.

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Haemichrome formation from haemoglobin subunits by hydrogen peroxide

Biochemical Journal ◽

10.1042/bj1710329 ◽

1978 ◽

Vol 171 (2) ◽

pp. 329-335 ◽

Cited By ~ 28

Author(s):

A Tomoda ◽

K Sugimoto ◽

M Suhara ◽

M Takeshita ◽

Y Yoneyama

Keyword(s):

Hydrogen Peroxide ◽

Superoxide Dismutase ◽

Glucose Oxidase ◽

Xanthine Oxidase ◽

Absorption Spectra ◽

Human Haemoglobin ◽

Kinetics Of

The effect of H2O2 on ferrous human haemoglobin subunits (alphash-, betash-, alphapmb- and betapmb-chains) was studied. These chains were easily transformed to haemichrome by the addition of H2O2 or H2O2-generating systems, including glucose oxidase (EC 1.1.3.4) AND XANTHINE OXIDASE (EC 1.2.3.2), and this was ascertained by e.p.r. measurements and by absorption spectra. The changes in these haemoglobin subunits were not inhibited by superoxide dismutase (EC 1.15.1.1), but were decreased by catalase (EC 1.11.1.6). The rate of oxidation of alphapmb-chains was higher than that of alphash-chains, and the rate of oxidation of betapmb-chains was higher than that of betash-chains. Haemichrome was demonstrated to be formed directly from these ferrous chains by the attack by H2O2, and this process did not involve formation of methaemoglobin. On the basis of these findings the kinetics of the reaction between the haemoglobin subunits and H2O2 was studied, and the pathological significance of H2O2 in disorders of erythrocytes such as thalassaemia was discussed.

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Lipid peroxidation of erythrocyte membrane induced by xanthine oxidase system: Modification of superoxide dismutase effect by hemoglobin.

Chemical and Pharmaceutical Bulletin ◽

10.1248/cpb.30.3662 ◽

1982 ◽

Vol 30 (10) ◽

pp. 3662-3668 ◽

Cited By ~ 18

Author(s):

TOSHIAKI MIURA ◽

TAKETO OGISO

Keyword(s):

Lipid Peroxidation ◽

Superoxide Dismutase ◽

Xanthine Oxidase ◽

Erythrocyte Membrane ◽

Oxidase System

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Stimulation of soluble guanylate cyclase by superoxide dismutase is mediated by NO

Biochemical Journal ◽

10.1042/bj3350527 ◽

1998 ◽

Vol 335 (3) ◽

pp. 527-531 ◽

Cited By ~ 24

Author(s):

Andreas FRIEBE ◽

Günter SCHULTZ ◽

Doris KOESLING

Keyword(s):

Superoxide Dismutase ◽

Xanthine Oxidase ◽

Guanylate Cyclase ◽

Soluble Guanylate Cyclase ◽

Hydroxyl Radical Scavengers ◽

Fold Activation ◽

Messenger Molecule ◽

Generating System ◽

Intercellular Messenger ◽

Stimulation Of

Soluble guanylate cyclase (sGC), which is found in many cells and tissues, represents the receptor for the intra- and intercellular messenger molecule NO. Superoxide dismutase (SOD), an enzyme involved in the degradation of toxic superoxide radicals, has been proposed as a non-NO activator of sGC. Here we show that SOD stimulated sGC purified from bovine lung up to 10-fold. Activation by SOD was not influenced by the hydroxyl radical scavengers mannitol and DMSO. In contrast, the presence of the NO scavengers oxyhaemoglobin and 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, as well as the O2--generating system xanthine oxidase/hypoxanthine, led to inhibition of SOD-stimulated cGMP production. NO-insensitive sGC mutants were not influenced either by SOD or by xanthine oxidase. We have previously shown that sGC was stimulated by NO present in the normal atmosphere. Here we show that the SOD effect depended on the NO concentration from the atmosphere, as the stimulation of sGC by defined NO gases (0, 120, 330 and 1000 parts per billion NO) was potentiated by SOD. NO stimulation of sGC and its potentiation by SOD were inhibited by oxyhaemoglobin to identical levels. We conclude that the SOD-mediated stimulation of sGC is due to the elimination of superoxide, thereby preventing its reaction with NO to form peroxynitrite.

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Nature of the oxygen species generated by xanthine oxidase involved in secretory histamine release from mast cells

Biochemistry and Cell Biology ◽

10.1139/o89-064 ◽

1989 ◽

Vol 67 (8) ◽

pp. 397-403 ◽

Cited By ~ 5

Author(s):

I. Aravind Menon ◽

Shaila Shirwadkar ◽

Narendranath S. Ranadive

Keyword(s):

Hydrogen Peroxide ◽

Superoxide Dismutase ◽

Mast Cells ◽

Xanthine Oxidase ◽

Cell Lysis ◽

Oxygen Species ◽

Hydrogen Peroxide Production ◽

Oxidase System ◽

Beneficial Effects ◽

Cellular Components

The present studies were carried out to characterize the nature of reactive oxygen species generated by the xanthine – xanthine oxidase system involved in the release of histamine by noncytotoxic and cytotoxic mechanisms. To distinguish secretory release from lytic release, mast cells were loaded with 51Cr and the release of 51Cr into the incubation medium was used as a measure of cell lysis. The secretory release of histamine was not inhibited by superoxide dismutase or catalase alone. However, together these agents inhibited the release. This suggests that the combination of superoxide and hydrogen peroxide can evoke secretory release. The lytic release of histamine, as monitored by concomitant release of 51Cr from mast cells at higher concentration of xanthine oxidase or longer periods of incubation, seems to be related to hydrogen peroxide production since catalase inhibited the cell lysis. Since it has been reported that exogenously added hydrogen peroxide at concentrations below 10 mM did not induce cell lysis, the lytic release, although hydrogen peroxide dependent, may not be due to its direct effect on the cell surface. The cell lysis observed in the xanthine – xanthine oxidase system seems to be brought about by a complex mechanism involving the interactions of hydrogen peroxide and superoxide with cellular components. These studies indicate that the beneficial effects of superoxide dismutase seen in biological systems may partly be due to inhibition of the secretory processes stimulated by superoxide.Key words: superoxide, hydrogen peroxide, mast cells, histamine, xanthine oxidase.

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Ultracytochemical localization of superoxide dismutase activity in rabbit alveolar macrophages: A comparative study using KO2 or xanthine-xanthine oxidase as O-2 generating system.

ACTA HISTOCHEMICA ET CYTOCHEMICA ◽

10.1267/ahc.19.263 ◽

1986 ◽

Vol 19 (2) ◽

pp. 263-275 ◽

Cited By ~ 3

Author(s):

MASARU KURODA

Keyword(s):

Superoxide Dismutase ◽

Comparative Study ◽

Xanthine Oxidase ◽

Alveolar Macrophages ◽

Superoxide Dismutase Activity ◽

Generating System

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Superoxide, Xanthine Oxidase and Platelet Reactions: Further Studies on Mechanisms by which Oxidants Influence Platelets

Thrombosis and Haemostasis ◽

10.1055/s-0038-1650190 ◽

1981 ◽

Vol 45 (03) ◽

pp. 290-293 ◽

Cited By ~ 9

Author(s):

Peter H Levine ◽

Danielle G Sladdin ◽

Norman I Krinsky

Keyword(s):

Superoxide Dismutase ◽

Cytochrome C ◽

Xanthine Oxidase ◽

Direct Effect ◽

Platelet Function ◽

Experimental Conditions ◽

Release Reaction

SummaryIn the course of studying the effects on platelets of the oxidant species superoxide (O- 2), Of was generated by the interaction of xanthine oxidase plus xanthine. Surprisingly, gel-filtered platelets, when exposed to xanthine oxidase in the absence of xanthine substrate, were found to generate superoxide (O- 2), as determined by the reduction of added cytochrome c and by the inhibition of this reduction in the presence of superoxide dismutase.In addition to generating Of, the xanthine oxidase-treated platelets display both aggregation and evidence of the release reaction. This xanthine oxidase induced aggreagtion is not inhibited by the addition of either superoxide dismutase or cytochrome c, suggesting that it is due to either a further metabolite of O- 2, or that O- 2 itself exerts no important direct effect on platelet function under these experimental conditions. The ability of Of to modulate platelet reactions in vivo or in vitro remains in doubt, and xanthine oxidase is an unsuitable source of O- 2 in platelet studies because of its own effects on platelets.

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