Biological Defense Mechanisms. THE PRODUCTION BY LEUKOCYTES OF SUPEROXIDE, A POTENTIAL BACTERICIDAL AGENT

Babior, Bernard M.; Kipnes, Ruby S.; Curnutte, John T.

doi:10.1172/jci107236

Cited by 2,694 publications

(1,044 citation statements)

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“…Monocytes play a crucial role in host defence by generating microbicidal oxygen metabolites including superoxide (O 2 2 ), hydrogen peroxide (H 2 O 2 ) and hydroxyl ions [20]. Phagocytosis by monocytes/ macrophages is associated with a respiratory burst, the phagocytosing cells increase oxygen uptake and thereby form H 2 O 2 and O 2 2 radicals [21].…”

Section: Discussionmentioning

confidence: 99%

Reactive oxygen intermediates, nitrite and IFN-γin Indian visceral leishmaniasis

Kumar

Pai

Sundar

2001

Clinical and Experimental Immunology

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SUMMARY Reactive oxygen intermediates (ROI), nitrite and interferon-gamma (IFN-γ) production were investigated at different times during treatment in 10 patients with visceral leishmaniasis (VL). Hydrogen peroxide (H2O2), superoxide (O2−) and IFN-γ production by cultured monocytes from patients with active VL were significantly lower compared with the healthy controls. In contrast, nitrite levels in the supernatants from monocyte cultures of VL patients were comparable to healthy controls and increased significantly during antileishmanial therapy. On day 20 of treatment, a significant increase in the release of H2O2, O2− and IFN-γ was observed. However, at follow-up, 4 months after the end of treatment, the production of H2O2, O2−, IFN-γ and nitrite had declined significantly. Thus, the impairment in hydrogen peroxide and superoxide production suggests that down-regulation of these mediators may be involved in the reduced killing of parasites by monocytes of active VL patients. Furthermore, the monocytes regained respiratory burst activity as the antileishmanial therapy progressed, suggesting that an immune-based mechanism is involved in successful drug therapy.

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Section: Discussionmentioning

confidence: 99%

Reactive oxygen intermediates, nitrite and IFN-γin Indian visceral leishmaniasis

Kumar

Pai

Sundar

2001

Clinical and Experimental Immunology

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“…2000) and immune function (Babior et al. 1973; Forman and Torres 2002), but in excess can cause DNA, lipid, and protein damage and disrupt cellular function (Harman 1956; Beckman and Ames 1998; Buffenstein et al. 2008).…”

Section: Introductionmentioning

confidence: 99%

Plasma markers of oxidative stress are uncorrelated in a wild mammal

Christensen

Selman

Blount

et al. 2015

Ecology and Evolution

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Oxidative stress, which results from an imbalance between the production of potentially damaging reactive oxygen species versus antioxidant defenses and repair mechanisms, has been proposed as an important mediator of life‐history trade‐offs. A plethora of biomarkers associated with oxidative stress exist, but few ecological studies have examined the relationships among different markers in organisms experiencing natural conditions or tested whether those relationships are stable across different environments and demographic groups. It is therefore not clear to what extent studies of different markers can be compared, or whether studies that focus on a single marker can draw general conclusions regarding oxidative stress. We measured widely used markers of oxidative damage (protein carbonyls and malondialdehyde) and antioxidant defense (superoxide dismutase and total antioxidant capacity) from 706 plasma samples collected over a 4‐year period in a wild population of Soay sheep on St Kilda. We quantified the correlation structure among these four markers across the entire sample set and also within separate years, age groups (lambs and adults), and sexes. We found some moderately strong correlations between some pairs of markers when data from all 4 years were pooled. However, these correlations were caused by considerable among‐year variation in mean marker values; correlation coefficients were small and not significantly different from zero after accounting for among‐year variation. Furthermore, within each year, age, and sex subgroup, the pairwise correlation coefficients among the four markers were weak, nonsignificant, and distributed around zero. In addition, principal component analysis confirmed that the four markers represented four independent axes of variation. Our results suggest that plasma markers of oxidative stress may vary dramatically among years, presumably due to environmental conditions, and that this variation can induce population‐level correlations among markers even in the absence of any correlations within contemporaneous subgroups. The absence of any consistent correlations within years or demographic subgroups implies that care must be taken when generalizing from observed relationships with oxidative stress markers, as each marker may reflect different and potentially uncoupled biochemical processes.

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“…The in¯ammation associated with these disorders is mediated following activation of tissue eosinophils which secrete a host of cytotoxic species including granule proteins and the activation of the NADPH oxidase complex ), a powerful oxidizing and reducing agent (Babior et al, 1973). In the presence of superoxide dismutase, O 2 7 dismutes to hydrogen peroxide (H 2 O 2 ) which can be subsequently converted into range of highly toxic free radicals .…”

Section: Introductionmentioning

confidence: 99%

Pharmacological comparison of LTB₄‐induced NADPH oxidase activation in adherent and non‐adherent guinea‐pig eosinophils

Lynch

Giembycz

Barnes

et al. 2001

British J Pharmacology

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1 Leukotriene B 4 (LTB 4 ) stimulation of guinea-pig peritoneal eosinophils, induced a biphasic activation of the NADPH oxidase composed of a rapid (53 min) phase mediated by non-adherent cells and a sustained (3 ± 120 min) phase mediated by CD11b/CD18 adherent eosinophils. Studies were undertaken to compare the intracellular mechanism that mediate these responses. 2 SB 203580 and PP1, inhibitors of p38 mitogen-activated protein (MAP) kinase and the src-family protein tyrosine kinases, respectively caused concentration-dependent attenuation of both the rapid (SB203580: pD 2 =76.31; PP1: pD 2 =75.50) and sustained (SB203580: pD 2 =76.50; PP1: pD 2 =75.73) phases. Similarly, the MAP kinase kinase-1 inhibitor, PD098059 produced partial inhibition of the both phases of superoxide generation. 3 The protein kinase C (PKC) inhibitors Ro-31 8220, GF 109203X and GoÈ 6976 attenuated the rapid NADPH oxidase response (pD 2 s=76.10, 76.72, 76.15 respectively) and, to a lesser extent, (pD 2 s=75.54, 76.02, 76.51 respectively) the sustained phase. 4 An inhibitor of phosphatidylinositol 3-kinase (PtdIns 3-kinase), wortmannin caused concentration dependent attenuation of the sustained (pD 2 =78.68) but not rapid phase of superoxide generation. In contrast, the syk kinase inhibitor, piceatannol abolished the rapid (pD 2 =76.43) but not sustained respiratory responses. 5 This study demonstrates that LTB 4 -induced superoxide generation from adherent and nonadherent eosinophils is mediated via both common (p38 MAP kinase, MEK-1, PKC and the src kinases) and divergent intracellular pathways (syk kinases and PtdIns 3-kinase). This suggests the possibility of therapeutic intervention to selective attenuate activation of adherent tissue eosinophils.

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Biological Defense Mechanisms. THE PRODUCTION BY LEUKOCYTES OF SUPEROXIDE, A POTENTIAL BACTERICIDAL AGENT

Cited by 2,694 publications

References 10 publications

Reactive oxygen intermediates, nitrite and IFN-γin Indian visceral leishmaniasis

Reactive oxygen intermediates, nitrite and IFN-γin Indian visceral leishmaniasis

Plasma markers of oxidative stress are uncorrelated in a wild mammal

Pharmacological comparison of LTB₄‐induced NADPH oxidase activation in adherent and non‐adherent guinea‐pig eosinophils

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Biological Defense Mechanisms. THE PRODUCTION BY LEUKOCYTES OF SUPEROXIDE, A POTENTIAL BACTERICIDAL AGENT

Cited by 2,694 publications

References 10 publications

Reactive oxygen intermediates, nitrite and IFN-γin Indian visceral leishmaniasis

Reactive oxygen intermediates, nitrite and IFN-γin Indian visceral leishmaniasis

Plasma markers of oxidative stress are uncorrelated in a wild mammal

Pharmacological comparison of LTB4‐induced NADPH oxidase activation in adherent and non‐adherent guinea‐pig eosinophils

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Pharmacological comparison of LTB₄‐induced NADPH oxidase activation in adherent and non‐adherent guinea‐pig eosinophils