Annexin-1 and Peptide Derivatives Are Released by Apoptotic Cells and Stimulate Phagocytosis of Apoptotic Neutrophils by Macrophages

Scannell, Michael; Flanagan, Michelle; deStefani, Andreas; Wynne, Kieran; Cagney, Gerard; Godson, Catherine; Maderna, P.

doi:10.4049/jimmunol.178.7.4595

Cited by 249 publications

(213 citation statements)

References 50 publications

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“…Many mediators can accelerate the clearance of apoptotic granulocytes mediated by macrophages, including AnxA1, IL-10, and proresolution lipids (2). The increased expression of GILZ and AnxA1 (15) observed during the resolution phase of inflammation may contribute to increase the efferocytic capacity of macrophages, an effect already demonstrated for AnxA1 (17,40).…”

Section: Discussionmentioning

confidence: 95%

The Role and Effects of Glucocorticoid-Induced Leucine Zipper in the Context of Inflammation Resolution

Vago

Tavares

Garcia

et al. 2015

The Journal of Immunology

108

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Glucocorticoid (GC)-induced leucine zipper (GILZ) has been shown to mediate or mimic several actions of GC. This study assessed the role of GILZ in self-resolving and GC-induced resolution of neutrophilic inflammation induced by LPS in mice. GILZ expression was increased during the resolution phase of LPS-induced pleurisy, especially in macrophages with resolving phenotypes. Pretreating LPS-injected mice with trans-activator of transcription peptide (TAT)–GILZ, a cell-permeable GILZ fusion protein, shortened resolution intervals and improved resolution indices. Therapeutic administration of TAT-GILZ induced inflammation resolution, decreased cytokine levels, and promoted caspase-dependent neutrophil apoptosis. TAT-GILZ also modulated the activation of the survival-controlling proteins ERK1/2, NF-κB and Mcl-1. GILZ deficiency was associated with an early increase of annexin A1 (AnxA1) and did not modify the course of neutrophil influx induced by LPS. Dexamethasone treatment resolved inflammation and induced GILZ expression that was dependent on AnxA1. Dexamethasone-induced resolution was not altered in GILZ−/− mice due to compensatory expression and action of AnxA1. Our results show that therapeutic administration of GILZ efficiently induces a proapoptotic program that promotes resolution of neutrophilic inflammation induced by LPS. Alternatively, a lack of endogenous GILZ during the resolution of inflammation is compensated by AnxA1 overexpression.

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Section: Discussionmentioning

confidence: 95%

The Role and Effects of Glucocorticoid-Induced Leucine Zipper in the Context of Inflammation Resolution

Vago

Tavares

Garcia

et al. 2015

The Journal of Immunology

108

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“…42,43 Furthermore, recognition of apoptotic neutrophils exerts additional anti-inflammatory effects because it leads back to inhibit the release of pro-inflammatory mediators and activate the production of anti-inflammatory IL-10 and TGF-␤. 44 -46 Many proinflammatory mediators, such as annexin A1, glucocorticoid, and lipoxin A 4 , have been shown to produce proefferocytic effects, [47][48][49] but no data are available with respect to MC receptor agonists. Using plate-based and validated in vivo protocols, 23,24 we observed that AP214 evoked a marked increase in the phagocytosis of human apoptotic neutrophils by cultured macrophages in vitro (with an increment of ϳ70%) and resident peritoneal macrophages in vivo (30%).…”

Section: Discussionmentioning

confidence: 99%

The Melanocortin Agonist AP214 Exerts Anti-Inflammatory and Proresolving Properties

Montero‐Melendez

Patel

Seed

et al. 2011

The American Journal of Pathology

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Synthetic and natural melanocortin (MC) peptides afford inhibitory properties in inflammation and tissue injury, but characterization of receptor involvement is still elusive. We used the agonist AP214 to test MC-dependent anti-inflammatory effects. In zymosan peritonitis, treatment of mice with AP214 (400 to 800 g/kg) inhibited cell infiltration, an effect retained in MC receptor type 1, or MC 1 , mutant mice but lost in MC 3 null mice. In vitro, cytokine release from zymosan-stimulated macrophages was affected by AP214, with approximately 80%, 30%, and 40% reduction in IL-1␤, tumor necrosis factor-␣, and IL-6, respectively. Inhibition of IL-1␤ release was retained in MC 1 mutant cells but was lost in MC 3 null cells. Furthermore, AP214 augmented uptake of zymosan particles and human apoptotic neutrophils by wild-type macrophages: this proresolving property was lost in MC 3 null macrophages. AP214 displayed its pro-efferocytotic effect also in vivo.

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“…Analyses of cell behavior indicated, besides defective recruitment, a direct impairment of phagocyte functions in Fpr2/3 −/− neutrophils. Although not in these settings, studies have demonstrated the importance of AnxA1, LXA 4 , and more recently resolvin D 1 in promoting particle phagocytosis and efferocytosis by immune cells (17,33,34) together with ineffectiveness in cells lacking Fpr2/3 (35).…”

Section: Discussionmentioning

confidence: 99%

Nonredundant protective properties of FPR2/ALX in polymicrobial murine sepsis

Gobbetti

Coldewey

Chen

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

104

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Significance Sepsis defines a syndrome with poor clinical management characterized by overlapping phases of excessive inflammation temporally aligned with an immunosuppressed state. We define an endogenous pathway centered on formyl-peptide receptor 2/3 (Fpr2/3)—ortholog to human FPR2/ALX (receptor for lipoxin A4)—that protects the host against polymicrobial sepsis. Using null mice and proof-of-concept experiments with a peptide–agonist, we demonstrate how engagement of Fpr2/3 is crucial to enact nonredundant functions that span from control of cell recruitment and phagocytosis, modulation of soluble mediator generation, to containment of bacteremia, thus preventing spreading to vital organs and opening new opportunities to manipulate the host response in sepsis.

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Annexin-1 and Peptide Derivatives Are Released by Apoptotic Cells and Stimulate Phagocytosis of Apoptotic Neutrophils by Macrophages

Abstract: The resolution of inflammation is a dynamically regulated process that may be subverted in many pathological conditions. Macrophage (

Cited by 249 publications

References 50 publications

The Role and Effects of Glucocorticoid-Induced Leucine Zipper in the Context of Inflammation Resolution

The Role and Effects of Glucocorticoid-Induced Leucine Zipper in the Context of Inflammation Resolution

The Melanocortin Agonist AP214 Exerts Anti-Inflammatory and Proresolving Properties

Nonredundant protective properties of FPR2/ALX in polymicrobial murine sepsis

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