Neutrophil respiratory burst is decreased in scleroderma and normalized by near-infrared mediated hyperthermia

Foerster, John; Storch, Annegret; Fleischanderl, S.; Wittstock, Stefan; Pfeiffer, Sebastian; Riemekasten, G.; Worm, Margitta

doi:10.1111/j.1365-2230.2006.02243.x

Cited by 15 publications

(6 citation statements)

References 17 publications

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“…The data are contradictory and are largely limited by old-fashioned neutrophil isolation procedures which can lead to neutrophil activation 16 17. A recent study has, however, shown that neutrophils produce less reactive oxygen species in vitro than control neutrophils when unstimulated 18. In agreement with this, we have found that neutrophils from patients with SSc are hypofunctional in tests of reactive oxygen species generation and chemotaxis (unpublished data).…”

Section: Introductionsupporting

confidence: 75%

Endothelial activation and apoptosis mediated by neutrophil-dependent interleukin 6 trans-signalling: a novel target for systemic sclerosis?

Barnes

Spiller

Anderson

et al. 2010

Annals of the Rheumatic Diseases

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ObjectivesSystemic sclerosis (SSc) is a connective tissue disease associated with significant morbidity and mortality and generally inadequate treatment. Endothelial cell activation and apoptosis are thought to be pivotal in the pathogenesis of this disease, but the mechanisms that mediate this remain unknown.MethodsHuman dermal microvascular endothelial cells were cultured with healthy control neutrophils in the presence of 25% healthy control or SSc serum for 24 h. Apoptosis was measured by annexin V-FITC binding and endothelial cell activation was measured using an allophycocyanin-conjugated E-selectin antibody. Fluorescence was quantified and localised using confocal microscopy.ResultsSSc serum resulted in significantly increased apoptosis (p=0.006) and E-selectin expression (p=0.00004) in endothelial cells compared with control serum, effects that were critically dependent on the presence of neutrophils. Recombinant interleukin 6 (IL-6) reproduced these findings. Immunodepletion of IL-6 and the use of an IL-6 neutralising antibody decreased the effect of SSc serum on E-selectin expression. Soluble gp130, which specifically blocks IL-6 trans-signalling, negated the effect of SSc serum on both E-selectin expression and apoptosis.ConclusionsSSc serum induces endothelial cell activation and apoptosis in endothelial cell-neutrophil co-cultures, mediated largely by IL-6 and dependent on the presence of neutrophils. Together with other pathologically relevant effects of IL-6, these data justify further exploration of IL-6 as a therapeutic target in SSc.

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Section: Introductionsupporting

confidence: 75%

Endothelial activation and apoptosis mediated by neutrophil-dependent interleukin 6 trans-signalling: a novel target for systemic sclerosis?

Barnes

Spiller

Anderson

et al. 2010

Annals of the Rheumatic Diseases

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“…In similarity with all inflammatory diseases, there is an increase in oxidative stress in blood and target tissue also in Ps and scleroderma but this should not necessarily be interpreted as a causative factor. In fact, it has been reported that the respiratory burst was reduced in neutrophils of scleroderma patients and a recent report of imiquimod‐induced psoriatic dermatitis showed a protective role by ROS, which was accompanied by increased IDO expression and Foxp3 + regulatory T‐cell frequency . Our findings suggest that mounting normal levels of ROS are vital in regulating the inflammatory response to mannan, otherwise this will lead to aberrant inflammation that precipitates in skin and joints.…”

Section: Ros Regulation Of Inflammatory Diseases – Innate Immunitysupporting

confidence: 57%

Ncf1 polymorphism reveals oxidative regulation of autoimmune chronic inflammation

Holmdahl

Sareila

Olsson

et al. 2015

Immunological Reviews

120

111

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The current review on the function of neutrophil cytosolic factor 1 (NCF1) and induced reactive oxygen species (ROS) is based on a genetic search for the major genes controlling autoimmune inflammatory disorders. Surprisingly, the disease-promoting allele determined a lower ROS response and was therefore in complete contrast to the prevailing dogma. Once cloned, it opened the possibility to dissect this complex field from a new angle and with the possibilities to study the role of ROS in vivo. We found that NCF1 and NADPH oxidase 2 (NOX2) complex-derived ROS is an important regulator of several chronic inflammatory disorders by using models for rheumatoid arthritis, multiple sclerosis, psoriasis and psoriasis arthritis, gout, and lupus. ROS could therefore affect many different types of diseases and the common denominator seems to be that ROS regulate macrophages, which prevents inflammation from going chronic. The role of ROS is currently changing from being seen as toxic agents that will promote inflammation toward a more complex view with ROS as crucial regulators of immune and inflammatory pathways.

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“…The data are contradictory and largely limited by old-fashioned neutrophil isolation procedures that can lead to neutrophil activation [9, 10]. A recent study has, however, shown that neutrophils produce less reactive oxygen species in vitro compared with control neutrophils when unstimulated [11]. In agreement with this we have found that neutrophils from patients with SSc are hypofunctional in tests of reactive oxygen species generation and chemotaxis (unpublished data).…”

Section: Introductionsupporting

confidence: 76%

Relative 1-anti-trypsin deficiency in systemic sclerosis

et al. 2011

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Objective. Neutrophil elastase is secreted by neutrophils during activation and circulates in the plasma where it can play a role in inflammation and fibrosis. This study examines the role of neutrophil elastase in SSc, a systemic CTD that is typified by vascular dysfunction, tissue fibrosis and inflammation.Methods. Serum neutrophil elastase and α1-anti-trypsin concentrations were assessed in SSc patients and healthy controls by ELISA. Serum neutrophil elastase activity was assessed by the elastase-dependent conversion of methoxy-succinyl-alanyl-alanyl-prolyl-valyl-p-nitroanilide to p-nitroanilide using a colourimetric assay. Elastase concentration and activity were correlated with clinical disease features.Results. Serum neutrophil elastase concentration and activity were equivalent in patients and controls; however, in SSc serum, there was an increase in elastase activity for each unit of elastase concentration (P = 0.03). This was due to a decrease in serum α1-anti-trypsin concentrations (P = 0.04). Serum elastase concentration (P = 0.03) and activity (P = 0.02) were significantly lower in RNP-positive patients and serum elastase concentrations were lower in ANA-positive patients (P = 0.003).Conclusions. Relative deficiency in serum α1-anti-trypsin concentrations in SSc could have important and pathogenically relevant effects since elastase has pro-inflammatory and pro-fibrotic roles. Elastase inhibitors are available in clinical practice and could represent potential therapeutic options in SSc.

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Neutrophil respiratory burst is decreased in scleroderma and normalized by near-infrared mediated hyperthermia

Cited by 15 publications

References 17 publications

Endothelial activation and apoptosis mediated by neutrophil-dependent interleukin 6 trans-signalling: a novel target for systemic sclerosis?

Endothelial activation and apoptosis mediated by neutrophil-dependent interleukin 6 trans-signalling: a novel target for systemic sclerosis?

Ncf1 polymorphism reveals oxidative regulation of autoimmune chronic inflammation

Relative 1-anti-trypsin deficiency in systemic sclerosis

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