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PubMed1984

Brucellacidal activity of human and bovine polymorphonuclear leukocyte granule extracts against smooth and rough strains of Brucella abortus.

The microbicidal activities of freeze-thaw and high-salt extracts of human and bovine polymorphonuclear leukocyte (PMN) granules were tested against a smooth intermediate strain (45/0) and a rough strain (45/20) of Brucella abortus which differ in virulence and survival within PMNs. Freeze-thaw extracts of human PMN granules were more brucellacidal than high-salt extracts when supplemented with hydrogen peroxide (H2O2) and potassium iodide (KI), whereas the opposite was found with freeze-thaw and high-salt extracts of bovine PMN granules. There was no oxygen-independent killing of either the smooth or rough strain of B. abortus by amounts of granule extracts which caused 100% killing of a deep rough mutant (Re) of Salmonella typhimurium. The oxygen-dependent brucellacidal activity of granule extracts was dependent on concentrations of myeloperoxidase (MPO) units, H2O2, and KI. Maximal brucellacidal activity was observed at pH 5.5 to 6.0. The smooth strain, 45/0, was more resistant to oxygen-dependent killing by granule extracts than was the rough strain, 45/20. Granule extracts were more brucellacidal than purified MPO at equivalent levels of MPO enzyme units, suggesting that at least one other reaction enhances killing by the MPO-H2O2-I- system.

Animals↗
PubMed1993

The effect of oxatomide on neutrophil oxygen radical generation.

The effect of oxatomide on reactive oxygen species (ROS) generated both by neutrophils and in a cell-free, xanthine-xanthine oxidase system was examined. The species investigated were superoxide radical anion (O2-), hydrogen peroxide (H2O2) and hydroxyl radical (OH.). Oxatomide significantly decreased neutrophil-generated O2-, H2O2 and OH. in a dose-dependent manner. H2O2 and OH. generated in a cell-free system were also reduced in the presence of oxatomide. The present study indicates that oxatomide decreases ROS generation presumably by inhibiting the neutrophil oxygen metabolism, and has the ability to scavenge H2O2 and OH.

Cell-Free System↗
PubMed1989

Effect of oxygen-derived free radicals and oxidants on the degradation in vitro of membrane phospholipids.

The abilities of chemically generated hydroxyl radical (OH.), superoxide anion (O.-) and hydrogen peroxide (H2O2) to degrade rat myocardial membrane phospholipids previously labeled with [1-14C]arachidonic acid were studied. HO. and H2O2, but not O2.-, caused the degradation of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylinositol (PI). With OH. and H2O2, the loss of radiolabel in PC was accompanied by an increase in the radiolabel of lysophosphatidylcholine (LPC), but not in that of free fatty acid (FFA). These results suggest the hydrolysis of 1-oxygen ester bond of PC by HO. and that H2O2 and that HO. and H2O2, but not O.-, are detrimental to the structure and function of membrane phospholipids. However, since microM amounts of HO. and mM amounts of H2O2 were necessary to affect the membrane phospholipids, it is likely that in the reperfused myocardium only HO., but not H2O2, may directly cause the breakdown of membrane phospholipids.

Animals↗
PubMed1991

The mixture of aldehydes and hydrogen peroxide produced in the ozonation of dioleoyl phosphatidylcholine causes hemolysis of human red blood cells.

Dioleoyl phosphatidylcholine (PC) liposomes were ozonized and the ozonized liposomes were tested for their lytic potency on human red blood cells (RBC). Ozonation of PC liposomes generated approximately 1 mole equivalent of hydrogen peroxide (H2O2) and 2 mole equivalents of aldehydes, based on the moles of ozone consumed. The time necessary for 50% hemolysis induced by ozonized liposomes (a convenient measure of hemolytic activity) was found to depend on the extent of ozonation of the PC liposomes, indicating the formation and accumulation of hemolytic agents during ozonation. Hemolysis was also observed when RBC were incubated with nonanal, the expected product of the ozonation of oleic acid, the principle unsaturated fatty acid in the liposomes. Hydrogen peroxide, another product of PC ozonation, did not induce hemolysis; however, a combination of H2O2 and nonanal was significantly more hemolytic than nonanal alone. A ratio of 1:2 H2O2/nonanal (the ratio observed in the ozonized liposomes) provided hemolytic activity comparable to that observed with ozonized dioleoyl PC. Among different antioxidants tested, ascorbate, catalase, and glutathione peroxidase partially inhibited hemolysis induced by ozonized liposomes and by H2O2/nonanal mixtures, but they were not protective against the nonanal-induced hemolysis. Identification of H2O2 and aldehydes as cytotoxic chemical species generated from the ozonation of unsaturated fatty acids may have an important bearing on the in vivo toxicity of ozone on the lung as well as on extrapulmonary tissues.

Aldehydes↗
PubMed1994

Erythrocyte catalase inactivation (H2O2 production) by ascorbic acid and glucose in the presence of aminotriazole: role of transition metals and relevance to diabetes.

Erythrocytes exposed to ascorbic acid in the presence of aminotriazole undergo a dose- and time-dependent inactivation of endogenous catalase which is proportional to environmental hydrogen peroxide (H2O2) concentrations. The production of H2O2 seems to be dependent upon the availability of transition metal chelatable by o-phenanthroline (OPT), although the kinetics of catalase inactivation and H2O2 production by externally added copper ions in the presence of OPT is complex. Furthermore, although glucose is also able to undergo a transition-metal-catalysed oxidation yielding H2O2, the production of H2O2 by glucose seems to be a minor process by comparison with ascorbic acid oxidation. Indeed, on the basis of these data, transition-metal-catalysed ascorbic acid oxidation is likely to be a more important source of oxidative stress in the diabetic state than hyperglycaemia.

Amitrole↗
PubMed1995

Hydroxyl radical generation by coal mine dust: possible implication to coal workers' pneumoconiosis (CWP).

Occupational exposure to coal mine dust causes coal workers' pneumoconiosis (CWP) and other pulmonary diseases by mechanisms that remain unclear. Because the hydroxyl radicals (.OH) may play an important role in the pathogenesis of CWP, we studied the potential role of bituminous coal mine dust samples for catalyzing the generation of .OH from hydrogen peroxide (H2O2). These coal mine dusts evaluated represented two geographic areas with diversity in CWP prevalence. Electron spin resonance (ESR), with the aid of spin trapping techniques, was used to measure the .OH radical generation. Bituminous coal mine dusts representing the Pittsburgh seam in the eastern United States and Blind Canyon seam in the mid-western United States were used together with a standard coal dust obtained from the National Institute of Standards and Technology, Gaithersburg, MD. All the coal mine dust samples generated varying levels of .OH radicals from H2O2 in the presence of a .OH spin trap 5,5-dimethyl-l-pyrroline-N-oxide (DMPO). .OH radical generation by the coal from H2O2 was effectively inhibited by deferoxamine and catalase, but only partially inhibited by superoxide dismutase. Metal chelators DETAPAC and EDTA enhanced the radical generation. These results indicated that the Fenton reaction is predominantly involved in the generation of .OH radicals from H2O2. The .OH-generating potential of all the coal dusts showed a positive correlation with the surface iron content of coal mine dusts. In addition, the potential to induce lipid peroxidation by the coal samples exhibited a good correlation with the available surface iron. Based on the results presented here, we propose that higher concentrations of surface iron in coal mine dust may be involved in the generation of increased levels of .OH radicals and may play an important role in the development of CWP in different coal mining areas.

Chelating Agents↗
PubMed1997

The effect of ethanol on sphincter of Oddi motility in vitro.

Antioxidant enzymes are present in nerves supplying the sphincter of Oddi and regulate its motor function. Oxygen free radicals (O2.-) produce hydrogen peroxide (H2O2) by the action of superoxide dismutase (SOD). Hydroxyl radical (OH.), an important mediator of H2O2 toxicity, oxidizes ETOH. Thus, the aim of our study was determine the effects of ETOH on sphincter of Oddi motility. The sphincter of Oddi was removed from opossums and force transducers recorded tension in its transverse axis. Alcohol (ETOH) was added to the tissue bath in concentrations from 0.1 to 0.4%. OH. was generated by the addition of 0.01% H2O2. Nitric oxide production was inhibited by the addition of 0.3 mM N omega-nitro-L-arginine (L-NNA). H2O2 increased the frequency of sphincter of Oddi contractions. Concentrations of ETOH > 0.3% decreased contractile frequency; however, 0.2% ETOH alone had no affect on the basal frequency of contraction but inhibited the increase in contractile frequency caused by H2O2. L-NNA also increased the contractile frequency; however, this effect was not inhibited by ETOH. We conclude that ETOH attenuates the effect of H2O2 on sphincter of Oddi motility.

Animals↗
PubMedDate not supplied

Role of cellular defense against hydrogen peroxide-induced inhibition of myocyte respiration.

Hydrogen peroxide (H2O2) serves as a precursor for highly reactive oxygen intermediates. However, the respiratory function of myocytes is relatively resistant to exogenously administered H2O2. In this study, we examined whether or not the reduction of cellular defense increases the toxicity of H2O2. Rat heart myocytes were isolated by collagenase digestion. Respiratory rates of myocytes, suspended in a medium containing sucrose, 3-N-morpholino-propanesulfonic acid, EGTA and bovine serum albumin, were determined polarographically in the presence of pyruvate and malate with or without 2,4-dinitrophenol (DNP). Mitochondrial membrane potentials were measured by using [3H]triphenylmethylphosphonium+. Cellular defense was attenuated by i) inhibiting the catalase activity by 3-amino-1,2,4-triazole (AT), ii) reducing the glutathione concentration by diethyl maleate (DEM) or ethacrinic acid (EA), and iii) permeabilizing the sarcolemmal membrane by saponin. The dose-response relationship between H2O2 (0.1-5 mM) and mitochondrial membrane potential was not greatly affected by these experimental conditions. Myocyte respiration was inhibited by 5 mM H2O2, particularly that measured in the presence of DNP (48% of control). DEM treatment did not significantly affect the respiratory inhibition by H2O2, whereas the degree of inhibition was somewhat greater following EA or AT treatment. By contrast, the sensitivity of cellular respiration to H2O2 was potentiated approximately two orders of magnitude by the permeabilization of sarcolemmal membrane; thus, 100 microM H2O2 inhibited both DNP-stimulated and unstimulated respiration to 17% and 35% of control, respectively. The results indicate that factors existing in the sarcolemma and/or in the cytosol, which become ineffective and/or are diluted, respectively, following permeabilization with saponin, are important cellular defense mechanisms in alleviating the toxic effect of exogenous H2O2 on the respiration of mitochondria in situ in myocytes.

Amitrole↗
PubMed1993

The antioxidant defense system of isolated guinea pig Leydig cells.

Utilization of highly enriched preparations of steroidogenic Leydig cells have proven invaluable for studying the direct effects of various hormones and agents on Leydig cell function in vitro. However, recent work indicates that isolated Leydig cells are often subjected to oxygen (O2) toxicity when cultured at ambient (19%) oxygen concentrations. Because intracellular antioxidants play an important role in protecting cells against oxygen toxicity, we have investigated the intracellular antioxidant defense system of isolated Leydig cells. The cellular levels of several antioxidants including catalase, glucose-6-phosphate dehydrogenase (G-6-PDH), superoxide dismutase (SOD) of the Cu/Zn & Mn variety, glutathione peroxidase, glutathione reductase and total glutathione were quantitated using enriched populations of Leydig cells isolated from adult male guinea pig testes. Compared to whole testicular homogenates, Leydig cells contained significantly (P < 0.01) less G-6-PDH, total SOD, glutathione reductase and total glutathione, but significantly (P < 0.001) more glutathione peroxidase. Compared to hepatic values previously reported in the guinea pig, Leydig cells contain nearly 400 times less catalase, about 14 times less glutathione peroxidase and almost 11 times less glutathione reductase. Since G-6-PDH and glutathione reductase are both necessary to regenerate reduced glutathione (GSH) which couples with glutathione peroxidase to breakdown hydrogen peroxide (H2O2) under normal conditions, it is plausible that the oxygen toxicity observed in isolated Leydig cells is due to the intracellular accumulation of H2O2.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1996

Superoxide and hydrogen peroxide-dependent inhibition of iron regulatory protein activity: a protective stratagem against oxidative injury.

Cellular iron homeostasis is regulated by the cytoplasmic iron regulatory protein (IRP), which binds to iron-responsive elements (IRE) of mRNAs, modulating iron uptake and sequestration, respectively. When iron is scarce, IRP binds to IRE and coordinately increases the synthesis of transferrin receptor and decreases that of ferritin, thus providing the cell with readily available free iron. When iron is in excess, IRP does not bind and iron sequestration prevails over iron uptake. We have found that incubation of rat liver lysates with xanthine oxidase (XO), which generates superoxide (O2-.) and hydrogen peroxide (H2O2), caused a remarkable but reversible inhibition of IRP activity, as the formation of IRE-IRP decreased by 70-80% but returned to baseline values upon exposure to a reducing agent like 2-mercaptoethanol. IRP inhibition was prevented by separate or simultaneous addition of superoxide dismutase and catalase, showing that both O2-. and H2O2 were involved. By contrast, iron chelators and hydroxyl radical scavengers did not impede the inhibition of IRP, suggesting that O2-. and H2O2 acted independently of free iron sources. Ferritin enhanced IRP inhibition, but this process involved tightly bound iron centers that shunted reducing equivalents from XO and returned them to oxygen, thus increasing the formation of O2-. In agreement with the exclusive role of O2-. and H2O2, XO also inhibited recombinant human IRP in the absence of iron. These results demonstrate that O2-. and H2O2 can directly but reversibly down-regulate the RNA-binding activity of IRP, causing transient decrease of free iron that otherwise would convert them into more potent oxidants such as hydroxyl radicals or equally aggressive iron-peroxo complexes. This establishes a novel protective stratagem against oxidative injury under pathophysiologic conditions characterized by the excessive generation of O2-. and H2O2.

Animals↗
PubMed1995

Hydrogen peroxide contracts human airways in vitro: role of epithelium.

The effects of hydrogen peroxide (H2O2) on human airway smooth muscle tone were determined in vitro. Treatment with H2O2 led to transient concentration-related contractions in the organ bath, amounting to 118 +/- 14 mg (mean +/- SE; n = 12) at 1 mM H2O2, and to greater and more prolonged contractions under superfusion conditions, amounting to 451 +/- 71 mg (n = 17) at 1 mM H2O2. Epithelial removal augmented the response to H2O2 in both systems. Addition of catalase (500 U/ml) abolished the effects of H2O2. Pretreatment of superfused tissues with indomethacin (3 microM) shifted the concentration-effect curve to H2O2 rightward and almost abolished the response to 1 mM H2O2 in epithelium-intact preparations (n = 16; P < 0.05); the response in epithelium-denuded tissues was also significantly inhibited (n = 16; P < 0.05). Pretreatment of the tissues with the TP prostanoid-receptor antagonist GR-32191B (1 microM) also inhibited the contractile effect of H2O2 in epithelium-intact and -denuded tissues. In separate experiments, H2O2 resulted in concentration-related generation of prostaglandin (PG) D2 from isolated airway preparations. The amount of PGD2 released was not different in tissues with intact epithelium compared with those without (n = 9; NS). We conclude that H2O2 exerts on isolated human airways a contractile effect that is augmented by epithelium removal and is largely mediated by prostanoids. The source of PGD2 does not appear to be the epithelium, which we suggest serves mainly as a barrier against H2O2-mediated bronchoconstriction.

Aged↗
PubMed1991

Isoproterenol prevents oxidant-induced injury in isolated rabbit lungs.

Increased vascular permeability in the adult respiratory distress syndrome is due in part to toxic oxygen metabolites. In the present study, we produced lung injury in the isolated rabbit lung with hydrogen peroxide (H2O2) and examined its prevention with isoproterenol. Pulmonary arterial pressure (Ppa) and the fluid filtration coefficient (Kf) were measured as indices of lung injury. Rabbits were divided into two groups, and 7 mmol/l H2O2 was administered in both groups. In one group, isoproterenol (2 micrograms/ml) was administered 10 min before H2O2 injury. Ppa increased transiently after H2O2 administration in the control group but was unchanged in the isoproterenol group. Kf was significantly increased by H2O2 administration in the control group but not in the isoproterenol group. We conclude that H2O2 increases pulmonary vascular permeability and that isoproterenol may protect against H2O2-induced pulmonary injury.

Animals↗
PubMed1994

Role of hydrogen peroxide in the inhibitory effect of ascorbate on cell growth.

Organ cultures have become an important method for the study of some of the biochemical reactions in which ascorbate takes part, and there are conflicting views on the stimulatory and inhibitory actions of ascorbate on cell growth. This study aimed to clarify the inhibitory mechanism of ascorbate using 3T6 fibroblasts. Cells were exposed to ascorbate at various concentrations in medium. The results showed that 3T6 fibroblasts were killed in medium containing more than 0.3 mM ascorbate. This lethal effect of ascorbate on cells was inhibited by the addition of catalase, an enzyme that decomposes hydrogen peroxide (H2O2), to the medium. When the medium with ascorbate was incubated in the absence of cells, the amount of H2O2 generation depended on the ascorbate concentration, and decreased in inverse proportion to the serum concentration added to the medium. The addition of albumin, which is the main protein in serum, also inhibited H2O2 generation in the medium with ascorbate. However H2O2 generation was not inhibited completely by serum and albumin. These results indicate that cytotoxicity of ascorbate is induced by H2O2.

3T3 Cells↗
PubMed1996

A positive correlation between catalase activity and ascorbate uptake in the tissues of guinea pigs and cultured cells of mammals.

We recently reported that the concentration of supplemental ascorbate which inhibits cell growth is positively related to intracellular catalase activity. It is assumed that the cells with high catalase activity are resistant to high concentrations of ascorbate since catalase can decompose hydrogen peroxide (H2O2) induced by the auto-oxidation of ascorbate in cultured medium. In this study, we investigated whether intracellular catalase activity affects the uptake of ascorbate into animal tissue and cultured cells. Ascorbate concentrations in the tissues of guinea pigs and various cultured cells, with and without supplementation of ascorbate, were determined to evaluate the efficiency of ascorbate uptake. We found a positive correlation between the efficiency of ascorbate uptake and catalase activity in various tissues of guinea pigs (r = 0.767, p < 0.05). Furthermore, a positive correlation between the two was also found in various species of cultured cells. This study indicates that tissues and cells with higher efficiency of ascorbate uptake are required for higher catalase activity, presumably for the decomposition of H2O2 from ascorbate.

Animals↗
PubMed1990

Similarities in the pharmacological modulation of reactive hyperemia and vasodilation to hydrogen peroxide in rat skeletal muscle arterioles: effects of probes for endothelium-derived mediators.

Our laboratory has demonstrated previously that prostaglandins are partially responsible for the vasodilation of rat cremaster muscle arterioles in vivo to a brief occlusion or hydrogen peroxide (H2O2). In the present study, in pentobarbital-anesthetized rats, we investigated the mechanism of the prostaglandin-independent portion of the dilation to these stimuli by measurement of changes in the diameter of third order cremasteric arterioles (approximately 15 microns) by video microscopy. In the presence of indomethacin suffusion (10 micrograms/ml), arteriolar dilation to the release of a 15-sec occlusion of a single arteriole or to topical application of 0.1 to 1 mM H2O2 (100 microliters) was reduced significantly by suffusion of 20 microM quinacrine or 5 microM methylene blue, whereas vasodilation to adenosine was not affected by these probes. Furthermore, the reactive hyperemia was not altered by suffusion of 50 microM hydroquinone or 0.2 mM NG-monomethyl-L-arginine, inhibitors of the dilation to acetylcholine mediated by the endothelium-derived relaxing factor. Reactive hyperemia was also not affected by 30 microM theophylline (an adenosine antagonist) or suffusion of catalase (160 U/ml) plus superoxide dismutase (240 U/ml). Therefore, the reactive hyperemia does not appear to be mediated through endothelium-derived relaxing factor, adenosine or the extracellular formation of reactive O2 species. However, these observations suggest that the prostaglandin-independent vasodilation to H2O2 and to the release of a brief arteriolar occlusion may be mediated by a common mechanism, possibly involving cyclic GMP. Similarities in pharmacological modulation of the dilation after occlusion and to H2O2 in the cremaster microcirculation suggest consideration of the involvement of H2O2 in the hyperemic response.

Animals↗
PubMed1991

Hydrogen peroxide alters the physical state and function of the plasma membrane of pulmonary artery endothelial cells.

Hydrogen peroxide (H2O2) is an important mediator of acute oxidative injury to vascular endothelium. Because the plasma membrane is the initial site of interaction between endothelial cells and extracellular H2O2 produced by stimulated neutrophils or macrophages, we evaluated the effect of H2O2 on the physical state, i.e., fluidity, and function of porcine pulmonary artery endothelial cell plasma membranes. Lactate dehydrogenase (LDH) release, 5-hydroxytryptamine (5-HT) uptake, limiting fluorescence anisotropy (r infinity) for trimethylamino-diphenylhexatriene (TMA-DPH), and conjugated dienes were measured 0.5, 6, and 24 hr after cells were exposed for 30 min to 50-microM H2O2 or Hank's Balanced Salt Solution (control). Compared with control cells, H2O2 caused significant increases in LDH release and in 5-HT uptake 6 hr after exposure. The increase in 5-HT uptake was not blocked by imipramine. H2O2 also caused a significant increase in r infinity for TMA-DPH 0.5 hr after exposure and a significant reduction in r infinity for TMA-DPH 6 hr after exposure. Cellular contents of conjugated dienes were increased 0.5 and 6 hr after exposure to H2O2. Twenty-four hours after exposure LDH release, r infinity, 5-HT uptake, and conjugated dienes had returned to control levels. Preincubation with 50-microM alpha-tocopherol (vitamin E) or 1-mM or 10-mM dimethylthiourea (DMTU) for 1 hr or 24 hr prevented endothelial cell injury, whereas addition of vitamin E or DMTU to the medium 1 hr or 3 hr after H2O2 exposure did not protect against injury. These results indicate that H2O2 causes significant damage to the plasma membrane of pulmonary artery endothelial cells in vitro, leading to alterations in fluidity and leakiness of the membrane. This injury is associated with membrane lipid peroxidation, is reversible, and can be prevented by pretreatment, but not by post-treatment, with vitamin E or DMTU.

Animals↗
PubMed1994

[Superoxide formation and lipid peroxidation by the mitochondrial electron-transfer chain].

Isolated mitochondria supplemented with succinate or NAD(+)-linked substrates generate hydrogen peroxide (H2O2) in State 4 and the generation is enhanced by antimycin A, an inhibitor of the respiratory chain. Superoxide is a stoichiometric precursor of mitochondrial H2O2 because the ratio of O2-/H2O2 generation rates is close to 2.0 and is generated by an autoxidizable component in the NADH dehydrogenase and the ubiquinone-cytochrome b site. Lipid peroxidation is a free radical-mediated degradation of polyunsaturated fatty acids. Lipid-peroxidation reactions by bovine submitochondrial particles are supported by NADH or NADPH in the presence of ADP-Fe3+ chelate. Electrons from NADH are supplied to the reactions from a component between the substrate site and the rotenone-sensitive site of the NADH dehydrogenase. The peroxidation is dependent on the rate of electron input into the respiratory chain and on the concentration of reduced ubiquinone. Alteration of inner-membrane components and damage to electron-transfer activities of submitochondrial particles are induced by lipid peroxidation. 1-Melhyl-4-phenylpyridinium (MPP+), a metabolite of a parkinsonism-inducing drug, induces NADH-dependent superoxide formation and enhances NADH-dependent lipid peroxidation in submitochondrial particles, indicating that the oxidative stress induced by MPP+ may potentiate its toxicity in dopamine neurons.

Electron Transport↗
PubMed1986

The effects of Con A-induced lymphokines from the T-lymphocyte subpopulations on human monocyte leishmanicidal capacity and H2O2 production.

The effects of concanavilin A (Con A)-induced lymphokines from human peripheral blood mononuclear cells, enriched helper and suppressor lymphocyte populations and recombinant interferon-gamma (IFN-gamma) on the ability of monocytes to promote killing of intracellular Leishmania major (L. major) amastigotes and to induce the production of hydrogen peroxide (H2O2) was examined. All these mitogen-induced supernatants contained active IFN-gamma. There were no differences in the ability of these supernatants or IFN-gamma to promote the monocyte killing of the L. major amastigotes or H2O2 production. An increase in H2O2 production by monocyte monolayers was observed following the addition of either of these supernatants or IFN-gamma alone. In addition, a marked increase in the production of H2O2 was observed following priming with either of these mitogen-induced supernatants or IFN-gamma and the addition of a second stimulus, phorbol myristate acetate (PMA). Monoclonal antibody to IFN-gamma abrogated the increase in production of H2O2 by all these mitogen-induced supernatants; however, this antibody only resulted in partial inhibition of the leishmaniacidal effect of these lymphokines on human monocytes. These results would suggest that IFN-gamma is the component of the lymphokine that is largely or exclusively responsible for H2O2 production, while other factors in addition to IFN-gamma are important in promoting oxygen-independent mechanisms for the killing of intracellular L. major amastigotes.

Cells, Cultured↗