Bactericidal Activity of Superoxide Anion and of Hydrogen Peroxide: Investigations Employing Dialuric Acid, a Superoxide-Generating Drug (original) (raw)
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Superoxide Dismutase Activity in Leukocytes
Journal of Clinical Investigation, 1974
dismutase activity has been identified in both human neutrophils and rabbit alveolar macrophages by two distinct assay procedures. The enzyme is insensitive to both cyanide and azide and is present in the cytosol of the cell. The identification of this enzyme in phagocytic cells is compatible with the theory that superoxide anion might be involved in the bactericidal activity of the cell. It is proposed that the enzyme functions to protect the cell against superoxide generated during the phagocytic process.
Escherichia coli from Antimicrobials Superoxide-Mediated Protection of
Updated information and services can be found at: These include: SUPPLEMENTAL MATERIAL Supplemental material REFERENCES http://aac.asm.org/content/57/11/5755#ref-list-1 at: This article cites 28 articles, 16 of which can be accessed free CONTENT ALERTS more» articles cite this article), Receive: RSS Feeds, eTOCs, free email alerts (when new http://journals.asm.org/site/misc/reprints.xhtml Information about commercial reprint orders: http://journals.asm.org/site/subscriptions/ To subscribe to to another ASM Journal go to: on March 28, 2014 by RUTGERS UNIVERSITY LIBR http://aac.asm.org/ Downloaded from on March 28, 2014 by RUTGERS UNIVERSITY LIBR http://aac.asm.org/
Journal of Experimental Medicine, 1984
We investigated the capacity of bacterial endotoxin (lipopolysaccharide, LPS) to modify the oxidative metabolic response to membrane stimulation of human neutrophils. Neutrophils were pretreated for 60 min with LPS, 10 ng/ml, then stimulated by exposure to fixed immune complexes, the chemotactic peptide formyl-methionyl-leucyl-phenylalanine (FMLP), or phorbol myristate acetate. Release of superoxide anion (O-2) was up to 7-times greater in cells preincubated with LPS, depending upon the stimulus used. Consumption of oxygen and release of hydrogen peroxide (H2O2) were similarly increased, using FMLP as stimulus. The enhancement was accompanied by a reduction in lag time and an increase in the rate of the response, but the duration of the oxidative events was not changed. The molecular basis for the augmented oxidative response of LPS-pretreated cells was investigated. Preincubation with LPS at 0 degrees C prevented priming, but preincubation in the presence of cycloheximide or chelat...
Aspects of the Release of Superoxide by Leukocytes, and a Means by Which This Is Switched off
Environmental Health Perspectives, 1994
Although great progress has been made in understanding the respiratory burst of leukocytes that produce superoxide (0-), it is possible that a component, or components, might have been overlooked. Furthermore, 0°production and its sequels, though cardinal in bactericidal action, might ultimately be damaging to the host's own cells. It is important, therefore, that a biologic mechanism exist to turn off 0°production by stimulated leukocytes. This article offers evidence that methoxatin (P00), a redox-cycling orthoquinone, might be involved in 0°production by leukocytes. This is based on the fact that inhibitors of 0°production, such as diphenylene iodonium (DPI) and 4,5-dimethylphenylene diamine (DIMPDA), were shown to sequester PQQ in leukocytes, i.e., to form adducts with that substance. Addition of PQQ to cells blocked with the inhibitors partially restored 0°release. With respect to turning off cellular°2 release, a factor was observed to be released to the medium by old macrophages (14 days old, but not by those less than 7 days old). Such conditioned medium, when added to stimulated neutrophils or macrophages, blocked 02 release. This factor was sensitive to proteases, exhibited molecular sizes of 3 and 11 kDa, and its action was independent of the nature of the stimulus applied to the leukocytes. It was partially purified by column (sizing) chromatography and HPLC. It seems to be a general modulator of the release of reactive oxygen species by phagocytes and is irrespective of phagocytic cellular type, or species from which the cells were derived.
Superoxide-Mediated Protection of Escherichia coli from Antimicrobials
Updated information and services can be found at: These include: SUPPLEMENTAL MATERIAL Supplemental material REFERENCES http://aac.asm.org/content/57/11/5755#ref-list-1 at: This article cites 28 articles, 16 of which can be accessed free CONTENT ALERTS more» articles cite this article), Receive: RSS Feeds, eTOCs, free email alerts (when new http://journals.asm.org/site/misc/reprints.xhtml Information about commercial reprint orders: http://journals.asm.org/site/subscriptions/ To subscribe to to another ASM Journal go to: on March 28, 2014 by RUTGERS UNIVERSITY LIBR http://aac.asm.org/ Downloaded from on March 28, 2014 by RUTGERS UNIVERSITY LIBR http://aac.asm.org/
The Journal of Immunology
gamma-Hexachlorocyclohexane was found to exert profound effects on the phosphatidylinositol cycle, cytosolic calcium level, and the respiratory burst of human neutrophils. Exposure of neutrophils prelabelled with 32P to 4 X 10(-4) M gamma-hexachlorocyclohexane almost tripled radioactivity in phosphatidic acid and correspondingly decreased radioactivity in phosphatidylinositol 4,5 bisphosphate. Under similar conditions, gamma-hexachlorocyclohexane evoked the generation of superoxide at a rate of over 11 nmol/min/10(6) cells and more than doubled cytosolic-free calcium concentration as monitored by Quin-2 fluorescence. Because intermediates of the phosphatidylinositol cycle, via increases in available calcium levels or activated protein kinase C, are considered potential second messengers for activation of the NADPH-dependent O-2-generating system, we compared neutrophil responses to gamma-hexachlorocyclohexane with responses to phorbol myristate acetate, an activator of protein kinase C with well known effects on neutrophils. Like phorbol myristate acetate, gamma-hexachlorocyclohexane induced neutrophil degranulation but was not an effective chemotactic stimulus. The ability of gamma-hexachlorocyclohexane to induce a pattern of oxidative activation in neutrophil cytoplasts similar to that in intact cells indicated that concurrent degranulation was not required for sustained O-2 generation in response to this agent. When neutrophils or neutrophil cytoplasts exposed to gamma-hexachlorocyclohexane were centrifuged and resuspended in stimulus-free medium, O-2 generation ceased entirely but could be reinitiated by addition of the same stimulus. This finding was in contrast to the continued O-2 production by phorbol myristate acetate-stimulated neutrophils similarly washed and resuspended in stimulus-free medium. Unlike subcellular fractions of phorbol myristate acetate-stimulated neutrophils, corresponding fractions prepared from gamma-hexachlorocyclohexane-stimulated neutrophils contained almost no detectable NADPH-dependent O-2-generating activity. Subcellular oxidase activity was not recovered when cells and membrane fractions were continuously exposed to gamma-hexachlorocyclohexane during disruption and fractionation after cell stimulation, nor could it be induced by the addition of the stimulus to the subcellular fractions. Thus, the stimulus dependence of continuous neutrophil superoxide release evoked by gamma-hexachlorocyclohexane does not merely reflect a physical interaction of the agonist with the enzyme system involved.(ABSTRACT TRUNCATED AT 400 WORDS)
Superoxide Radicals, Superoxide Dismutases and the Aerobic Lifestyle
Photochemistry and Photobiology, 1978
The superoxide radical (0;) is a commonplace product of the biological reduction of molecular oxygen and plays an important role in oxygen toxicity. Superoxide dismutases (SOD) catalytically scavenge this radical and are the primary defense against its cytotoxicity. The data which support these statements have been briefly reviewed. Oxygen enhances the lethality of certain antibiotics, such as streptonigrin, and of ionizing radiation as well. The role of 0; in the enhancements is presented and the basis of the radioprotective effects of SOD discussed. Several more recent developments are presented in detail including: (a) The induction of the MnSOD of E. coli upon exposure to very low levels of oxygen. (b) The changes in SOD in E. coli as a function of nutritional state, during culture in a chemostat. (c) A convenient new assay and activity stain for SOD.
Effect of nitric oxide on staphylococcal killing and interactive effect with superoxide
Infection and Immunity, 1996
The role of reactive nitrogen intermediates (RNI) such as nitric oxide (.NO) in host defense against pyogenic microorganisms is unclear, and the actual interactive effect of RNI and reactive oxidative intermediates (ROI) for microbial killing has not been determined. Since, in nature, ROI and RNI might be generated together within any local infection, we evaluated the separate and interactive effects of .NO and O2- on staphylococcal survival by using a simplified system devoid of eukaryotic cells. These studies showed that prolonged exposure of staphylococci to .NO does not result in early loss of viability but instead is associated with a dose-related delayed loss of viability. This effect is abrogated by the presence of hemoglobin, providing further evidence that the effect is RNI associated. Superoxide-mediated killing also is dose related, but in contrast to RNI-mediated killing, it is rapid and occurs within 2 h of exposure. We further show that the interaction of .NO and O(2)-...