Coupling of neutrophil apoptosis to recognition by macrophages: coordinated acceleration by protein synthesis inhibitors

Whyte, Moira K. B.; Savill, John; Meagher, Laura C.; Lee, Alison; Haslett, Christopher

doi:10.1002/jlb.62.2.195

Cited by 67 publications

(41 citation statements)

References 42 publications

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“…2, B and C). When protein biosynthesis was blocked by the addition of cycloheximide, apoptosis was significantly increased to over 75% (Ϯ10%, n ϭ 5, p Ͻ0.01) as has been reported previously (25)(26)(27). The addition of GM-CSF significantly decreased the number of apoptotic cells to 15% (Ϯ8%, n ϭ 5); importantly, inhibition of the proteasome by use of the inhibitor MG-132 also significantly decreased the rate of apoptosis of neutrophils.…”

Section: Effects Of Proteasome Inhibition On Mcl-1 Levels and Apoptossupporting

confidence: 79%

Granulocyte Macrophage Colony-stimulating Factor Signaling and Proteasome Inhibition Delay Neutrophil Apoptosis by Increasing the Stability of Mcl-1

Derouet

Thomas

Cross

et al. 2004

Journal of Biological Chemistry

214

205

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Section: Effects Of Proteasome Inhibition On Mcl-1 Levels and Apoptossupporting

confidence: 79%

Granulocyte Macrophage Colony-stimulating Factor Signaling and Proteasome Inhibition Delay Neutrophil Apoptosis by Increasing the Stability of Mcl-1

Derouet

Thomas

Cross

et al. 2004

Journal of Biological Chemistry

214

205

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“…To block protein synthesis cycloheximide was titrated to low concentrations to minimize the induction of neutrophil apoptosis that has been reported by this compound (43). Apoptosis was assessed by morphology and annexin V binding following overnight culture of neutrophils with Bt 2 cAMP and cycloheximide (Fig.…”

Section: Camp Regulator Neutrophil Apoptosis Via a Novel Pathwayretarmentioning

confidence: 99%

Cyclic AMP Regulation of Neutrophil Apoptosis Occurs via a Novel Protein Kinase A-independent Signaling Pathway

Martin

Dransfield

Haslett

et al. 2001

Journal of Biological Chemistry

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101

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The second messenger molecule cyclic AMP dramatically modulates the apoptotic program in a wide variety of cells, accelerating apoptosis in some and delaying the rate of apoptosis in others. Human neutrophil apoptosis, a process that regulates the fate and numbers of these potentially histotoxic cells in inflammatory sites, is profoundly delayed by the cell-permeable analog of cyclic AMP, dibutyryl-cAMP. We have investigated the mechanisms underlying cyclic AMP-mediated delay of neutrophil apoptosis, and we show that cyclic AMP inhibits loss of mitochondrial potential occurring during constitutive neutrophil apoptosis. Furthermore, we demonstrate that cyclic AMP also suppresses caspase activation in these inflammatory cells. Despite increasing protein kinase A activity, this kinase is unlikely to mediate the effect of cyclic AMP on apoptosis because blockade of protein kinase A activation did not influence the survival effects of cyclic AMP. Further investigation of the signaling mechanism demonstrated that the delay of apoptosis is independent of phosphoinositide 3-kinase and MAPK activation. Our results suggest cyclic AMP delays neutrophil apoptosis via a novel, reversible, and transcriptionally independent mechanism. We show that proteasome activity in the neutrophil is vitally involved in this process, and we suggest that a balance of pro-apoptotic and anti-apoptotic proteins plays a key role in the powerful ability of cyclic AMP to delay neutrophil death.

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“…Apoptotic cell death has been proposed as a central mechanism underlying the ordered elimination of neutrophils from an inflammatory site and, hence, to play a key role in the resolution of inflammation [1,2]. Dysregulation of this process by various inflammatory mediators may contribute directly to the pathogenesis of several diseases characterized by neutrophil-mediated tissue injury, including acute respiratory distress syndrome (ARDS) [3,4].…”

Section: Introductionmentioning

confidence: 99%

The survival effect of TNF‐α in human neutrophils is mediated via NF‐κB‐dependent IL‐8 release

et al. 2004

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The capacity of cytokines to modulate neutrophil apoptosis is thought to be a major factor influencing the resolution of granulocytic inflammation. We have previously shown that the late survival effect of TNF‐α in human neutrophils involves activation of both NF‐κB and phosphoinositide 3‐kinase (PI3‐kinase) pathways. In this study, we address how these pathways integrate to prevent cell death. In human neutrophils, TNF‐α (200 U/ml) induced rapid IκB‐α degradation, NF‐κB activation and IL‐8 release (31.8±5.4 pg/105 cells/2 h), whereas GM‐CSF (10 ng/ml) stimulated an equivalent IL‐8 release (26.5±4.5 pg/105 cells/2 h) without enhanced IκB‐α degradation or NF‐κB activation compared to control. Importantly, inhibition of PI3‐kinase did not modify TNF‐α ‐induced IκB‐α degradation, yet fully inhibited the survival effect of both cytokines. Inhibition of IκB‐α phosphorylation, PI3‐kinase or ERK1/2 activation blocked IL‐8 release by both cytokines. Blocking IL‐8 activity by inhibiting its synthesis or by using a neutralizing antibody enhanced the early pro‐apoptotic effectof TNF‐α and inhibited its late survival effect without affecting GM‐CSF‐induced survival. These data suggest that cross‐talk between NF‐κB and PI3‐kinase pathways in TNF‐α ‐stimulated neutrophils results from NF‐κB/ERK1/2‐dependent IL‐8 production which acts in an autocrine manner to drive PI3‐kinase‐dependent survival. In contrast, GM‐CSF‐mediated survival does not involve NF‐κB activation or IL‐8 release.

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Coupling of neutrophil apoptosis to recognition by macrophages: coordinated acceleration by protein synthesis inhibitors

Abstract: Abstract:Onset ofapoptosis in many cell types, includ

Cited by 67 publications

References 42 publications

Granulocyte Macrophage Colony-stimulating Factor Signaling and Proteasome Inhibition Delay Neutrophil Apoptosis by Increasing the Stability of Mcl-1

Granulocyte Macrophage Colony-stimulating Factor Signaling and Proteasome Inhibition Delay Neutrophil Apoptosis by Increasing the Stability of Mcl-1

Cyclic AMP Regulation of Neutrophil Apoptosis Occurs via a Novel Protein Kinase A-independent Signaling Pathway

The survival effect of TNF‐α in human neutrophils is mediated via NF‐κB‐dependent IL‐8 release

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