Rheumatoid peripheral blood phagocytes are primed for activation but have impaired Fc-mediated generation of reactive oxygen species

Fairhurst, Anna‐Marie; Wallace, Paul K.; Jawad, Ali S M; Goulding, N J

doi:10.1186/ar2144

Cited by 20 publications

(15 citation statements)

References 58 publications

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“…The assessment of chemiluminescence produced by one neutrophil confirmed that neutrophils of arthritic rats responded excessively to PMA stimulation and synthesized more radicals than neutrophils of healthy controls. A similar priming of peripheral neutrophils was observed in [38][39][40] . These alterations were ascribed to the direct effect of proinflammatory cytokines on neutrophil NADPH oxidase activity, which was induced by the increased phosphorylation of p47 phox , extracellular signal-regulated kinase, and p38 mitogen-activated protein kinase [39,41] .…”

Section: Discussionsupporting

confidence: 55%

The natural stilbenoid pinosylvin and activated neutrophils: effects on oxidative burst, protein kinase C, apoptosis and efficiency in adjuvant arthritis

et al. 2012

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Aim: To investigate the effects of the naturally occurring stilbenoid pinosylvin on neutrophil activity in vitro and in experimental arthritis, and to examine whether protein kinase C (PKC) activation served as an assumed target of pinosylvin action. Methods: Fresh human blood neutrophils were isolated. The oxidative burst of neutrophils was evaluated on the basis of enhanced chemiluminescence. Neutrophil viability was evaluated with flow cytometry, and PKC phosphorylation was assessed by Western blotting analysis. Adjuvant arthritis was induced in Lewis rats with heat-killed Mycobacterium butyricum, and the animals were administered with pinosylvin (30 mg/kg, po) daily for 21 d after arthritis induction. Results: In isolated human neutrophils, pinosylvin (10 and 100 µmol/L) significantly decreased the formation of oxidants, both extraand intracellularly, and effectively inhibited PKC activation stimulated by phorbol myristate acetate (0.05 µmol/L). The inhibition was not due to neutrophil damage or increased apoptosis. In arthritic rats, the number of neutrophils in blood was dramatically increased, and whole blood chemiluminescence (spontaneous and PMA-stimulated) was markedly enhanced. Pinosylvin administration decreased the number of neutrophils (from 69 671±5588/µL to 51 293±3947/µL, P=0.0198) and significantly reduced the amount of reactive oxygen species in blood. Conclusion: Pinosylvin is an effective inhibitor of neutrophil activity, and is potentially useful as a complementary medicine in states associated with persistent inflammation.

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Section: Discussionsupporting

confidence: 55%

The natural stilbenoid pinosylvin and activated neutrophils: effects on oxidative burst, protein kinase C, apoptosis and efficiency in adjuvant arthritis

et al. 2012

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“…However, there is a need to re-evaluate these data and to consider whether complement receptors are activated in RA neutrophils. Recent evidence suggests that neutrophils from RA patients have a functional impairment in FcRgIIa-and FcRgIIIb-mediated ROS production compared to age-and sex-matched controls (65). In this latter study, the defect in neutrophils from RA patients to produce ROS upon FcgIIa=FcgIIIb heterologous crosslinking was not a consequence of changes in FcgIIa=FcgIIIb expression, since identical levels of FcgIIa=FcgIIIb were observed in neutrophils from RA patients when compared to controls (65).…”

mentioning

confidence: 67%

“…Recent evidence suggests that neutrophils from RA patients have a functional impairment in FcRgIIa-and FcRgIIIb-mediated ROS production compared to age-and sex-matched controls (65). In this latter study, the defect in neutrophils from RA patients to produce ROS upon FcgIIa=FcgIIIb heterologous crosslinking was not a consequence of changes in FcgIIa=FcgIIIb expression, since identical levels of FcgIIa=FcgIIIb were observed in neutrophils from RA patients when compared to controls (65). Collectively these data suggest that neutrophils from RA patients may have impaired amplification of Fcg receptor function that contribute to neutrophil hyporesponsiveness and further exacerbate the susceptibility and morbidity to infection.…”

mentioning

confidence: 99%

Aberrant Reactive Oxygen and Nitrogen Species Generation in Rheumatoid Arthritis (RA): Causes and Consequences for Immune Function, Cell Survival, and Therapeutic Intervention

Phillips

Dias

Kitas

et al. 2010

Antioxidants & Redox Signaling

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The infiltration and persistence of hematopoietic immune cells within the rheumatoid arthritis (RA) joint results in elevated levels of pro-inflammatory cytokines, increased reactive oxygen (ROS) and -nitrogen (RNS) species generation, that feeds a continuous self-perpetuating cycle of inflammation and destruction. Meanwhile, the controlled production of ROS is required for signaling within the normal physiological reaction to perceived "foreign matter" and for effective apoptosis. This review focuses on the signaling pathways responsible for the induction of the normal immune response and the contribution of ROS to this process. Evidence for defects in the ability of immune cells in RA to regulate the generation of ROS and the consequence for their immune function and for RA progression is considered. As the hypercellularity of the rheumatoid joint and the associated persistence of hematopoietic cells within the rheumatoid joint are symptomatic of unresponsiveness to apoptotic stimuli, the role of apoptotic signaling proteins (specifically Bcl-2 family members and the tumor suppressor p53) as regulators of ROS generation and apoptosis are considered, evaluating evidence for their aberrant expression and function in RA. We postulate that ROS generation is required for effective therapeutic intervention.

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“…These ICs were used in the assay systems as suspensions, having been gently homogenized by inversion immediately before use. It is noteworthy that an IC formed by an antibody produced in rabbits is efficient stimulus for human neutrophils activation, as reported in the literature [22,[32][33][34].…”

Section: Immune Complex (Ic)mentioning

confidence: 52%

Activation of Complement Alternative Pathway in Rheumatoid Arthritis: Implications in Peripheral Neutrophils Functions

Paoliello-Paschoalato¹

2011

TOAUTOJ

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Evaluation of the respiratory burst induced by receptors Fc R and CR was carried out in peripheral blood neutrophils (PBN) in rheumatoid arthritis (RA) patients with active and inactive disease. Simultaneously, cooperation between these receptors and their expression, PBN chemotaxis, and complement system systemic activity were also investigated. Neutrophils were stimulated with IC-IgG opsonized with normal human serum (NHS) or not, or with IC-IgG opsonized with RA human serum (RAHS). ROS production was increased in neutrophils of patients with active or inactive RA stimulated of IC-IgG opsonized with NHS compared to the response of the cells mediated by ICIgG. However, there was poor Fc R/CR cooperation in these RA neutrophils, as indicated by decreased ROS production upon stimulation with IC-IgG opsonized with RAHS. In the case of active RA patients, neutrophils presented significantly higher CR1 and CR3 expression, as well as slight elevation in CD32 and CD16 expression. Positive correlations between Fc R and CR, complement alternative pathway activation, and increased RA serum chemotaxic activity were only detected in active RA patients. Taken together, these results indicate that several abnormalities of the complement system exist at the systemic level, namely impaired membrane receptor cooperation, alternative pathway activation, and presence of pre-existing chemoattractant factors in the serum, as reflected by the neutrophil function in the particular case of active RA patients. All, these abnormalities may synergistically contribute to RA pathogenesis.

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Rheumatoid peripheral blood phagocytes are primed for activation but have impaired Fc-mediated generation of reactive oxygen species

Abstract: Significant levels of circulating immune complexes (ICs)

Cited by 20 publications

References 58 publications

The natural stilbenoid pinosylvin and activated neutrophils: effects on oxidative burst, protein kinase C, apoptosis and efficiency in adjuvant arthritis

The natural stilbenoid pinosylvin and activated neutrophils: effects on oxidative burst, protein kinase C, apoptosis and efficiency in adjuvant arthritis

Aberrant Reactive Oxygen and Nitrogen Species Generation in Rheumatoid Arthritis (RA): Causes and Consequences for Immune Function, Cell Survival, and Therapeutic Intervention

Activation of Complement Alternative Pathway in Rheumatoid Arthritis: Implications in Peripheral Neutrophils Functions

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