Regulation of neutrophil apoptosis via death receptors

Akgül, Cahit; Edwards, Steven W.

doi:10.1007/s00018-003-3110-z

Cited by 76 publications

(68 citation statements)

References 48 publications

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“…This may in turn trigger the activation of NF-B and activator protein 1, which may induce the expression of survival factors, thus providing resistance against apoptosis. The response of the neutrophil to TNF␣ is very much concentrationdependent (35,36). In our present study, TNF␣ levels were observed to be low in juvenile-onset SLE sera compared with control sera.…”

Section: Role Of Neutrophil Apoptosis In Juvenile-onset Sle 2397supporting

confidence: 49%

“…It is therefore unlikely that a single factor in juvenile-onset SLE sera is responsible for the enhanced neutrophil apoptosis, but rather, that a combination of these factors leads to enhanced cell death. Exposure of cells to TNF␣ can induce multiple effects, including cell differentiation, proliferation, apoptosis, and other proinflammatory effects (35). TNF␣ can induce apoptosis through TNF receptor I in some cell types, including neutrophils.…”

Section: Role Of Neutrophil Apoptosis In Juvenile-onset Sle 2397mentioning

confidence: 99%

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The role of neutrophil apoptosis in juvenile‐onset systemic lupus erythematosus

Midgley¹,

McLaren²,

Moots³

et al. 2009

Arthritis & Rheumatism

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Objective. Accumulation of apoptotic cells may lead to the development of systemic lupus erythematosus (SLE) through a breakdown in immune tolerance. Altered neutrophil apoptosis may contribute to nuclear autoantigen exposure, ultimately leading to autoantibody generation. This study aimed to determine whether neutrophil apoptosis is altered in patients with juvenileonset SLE as compared with controls.Methods. Apoptosis was measured in neutrophils from patients with juvenile-onset SLE (n ‫؍‬ 12), adultonset SLE (n ‫؍‬ 6), and pediatric patients with inflammatory (n ‫؍‬ 12) and noninflammatory (n ‫؍‬ 12) conditions. Annexin V staining and flow cytometry were used to determine neutrophil apoptosis. Proapoptotic and antiapoptotic proteins were measured in sera and in neutrophil cell lysates.Results. Neutrophil apoptosis was significantly increased in patients with juvenile-onset SLE as compared with the noninflammatory controls at time 0. Incubation of neutrophils with sera from patients with juvenile-onset SLE further increased neutrophil apoptosis as compared with incubation with sera from pediatric controls. Concentrations of TRAIL and FasL were significantly increased in sera from patients with juvenile-onset SLE, whereas interleukin-6, tumor necrosis factor ␣, and granulocyte-macrophage colonystimulating factor (GM-CSF) were significantly decreased. Addition of GM-CSF to sera from patients with juvenile-onset SLE significantly decreased neutrophil apoptosis as compared with juvenile-onset SLE sera alone. The expression of proapoptotic proteins (caspase 3, Fas, and FADD) was elevated in juvenile-onset SLE neutrophils, whereas the expression of antiapoptotic proteins (cellular inhibitor of apoptosis 1 and 2 and X-linked inhibitor of apoptosis) was decreased. Neutrophil apoptosis correlated with biomarkers of disease activity (erythrocyte sedimentation rate and doublestranded DNA concentration) and the British Isles Lupus Assessment Group disease activity score.Conclusion. Our data demonstrate an imbalance in proapoptotic and antiapoptotic factors in both neutrophils and sera from patients with juvenile-onset SLE. This imbalance results in increased neutrophil apoptosis in these patients. Correlations with markers of disease activity indicate that altered neutrophil apoptosis in juvenile-onset SLE patients may play a pathogenic role in this condition.Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with a wide spectrum of clinical and immunologic abnormalities (1) that is characterized by hyperactive B cells that produce a range of autoantibodies. Although the cause of SLE remains unknown, a complex interplay between genetic and environmental factors appears to contribute to its immunopathogenesis. Autoantigens typical of SLE (e.g., Ro, La, double-stranded DNA [dsDNA], RNP, etc.) are clustered in blebs on the surface of apoptotic cells (2). Adult patients with SLE show increased apoptosis and defective clearance of monocytes and lymphocytes (3), as well as increased neutrophil apoptosis (4)....

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Section: Role Of Neutrophil Apoptosis In Juvenile-onset Sle 2397supporting

confidence: 49%

Section: Role Of Neutrophil Apoptosis In Juvenile-onset Sle 2397mentioning

confidence: 99%

The role of neutrophil apoptosis in juvenile‐onset systemic lupus erythematosus

Midgley¹,

McLaren²,

Moots³

et al. 2009

Arthritis & Rheumatism

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“…Fas is a quintessential death receptor in neutrophils (28,29), and it is known to stimulate ectodomain shedding (12)(13)(14). Because Fas-mediated signaling events do not always involve caspases (30,31), we initially examined their requirement in ADAM17 stimulation.…”

Section: Resultsmentioning

confidence: 99%

Different Signaling Pathways Stimulate a Disintegrin and Metalloprotease-17 (ADAM17) in Neutrophils during Apoptosis and Activation

Wang

Robertson

Walcheck

2011

Journal of Biological Chemistry

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Background: Neutrophil ADAM17 (a disintegrin and metalloprotease-17) mediates the proteolytic release of receptors and soluble factors that regulate inflammation. Results: ADAM17 stimulation during Fas-induced neutrophil apoptosis requires caspase-8, Bid, and mitochondrial reactive oxygen species. Conclusion: Neutrophil ADAM17 stimulation occurs by different signal transduction pathways during activation and apoptosis. Significance: ADAM17 activation in apoptotic neutrophils may rapidly down-regulate their pro-inflammatory activity.

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“…In contrast to other proinflammatory mediators, TNFa is a unique cytokine which possesses both proapoptotic and antiapoptotic activity, depending on the intracellular and extracellular environment [108]. Survival is usually induced at low doses of TNFa, while proapoptotic effects were observed at high doses [109].…”

Section: Tnfamentioning

confidence: 99%

Constitutive neutrophil apoptosis: Mechanisms and regulation

2007

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Neutrophil constitutive death is a critical cellular process for modulating neutrophil number and function, and it plays an essential role in neutrophil homeostasis and the resolution of inflammation. Neutrophils die due to programmed cell death or apoptosis. In this article, we review recent studies on the mechanism of neutrophil apoptosis. The involvement of caspase, calpain, reactive oxygen species, cellular survival/death signaling pathways, mitochondria, and BCL-2 family member proteins are discussed. The fate of neutrophils can be influenced within the inflammatory microenvironment. We summarize the current understanding regarding the modulation of neutrophil apoptotic death by various extracellular stimuli such as proinflammatory cytokines, cell adhesion, phagocytosis, red blood cells, and platelets. The involvement of neutrophil apoptosis in infectious and inflammatory diseases is also addressed. Am. J. Hematol. 83:288-295, 2008. V

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Regulation of neutrophil apoptosis via death receptors

Cited by 76 publications

References 48 publications

The role of neutrophil apoptosis in juvenile‐onset systemic lupus erythematosus

The role of neutrophil apoptosis in juvenile‐onset systemic lupus erythematosus

Different Signaling Pathways Stimulate a Disintegrin and Metalloprotease-17 (ADAM17) in Neutrophils during Apoptosis and Activation

Constitutive neutrophil apoptosis: Mechanisms and regulation

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