Adhesion-induced eosinophil cytolysis requires the receptor-interacting protein kinase 3 (RIPK3)–mixed lineage kinase-like (MLKL) signaling pathway, which is counterregulated by autophagy

Radonjic-Hoesli, Susanne; Wang, Xiaoliang; Graauw, Elisabeth de; Stoeckle, Christina; Styp-Rekowska, Beata; Hlushchuk, Ruslan; Simon, Dagmar; Spaeth, Peter; Yousefi, Shída; Simon, Hans‐Uwe

doi:10.1016/j.jaci.2017.01.044

Cited by 55 publications

(60 citation statements)

References 51 publications

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“…If the source of infection/stimulation persists, the released mtDNA, having similarity to viral and bacterial DNA (enriched in unmethylated CpG motifs), acts as a danger signal and triggers cytokine production for a protective and regulated immune response 7,55 . b Cytolysis: Under pathological conditions, such as the persistent presence of foreign antigens 104 , "too large to be trapped antigens", such as fungal hyphae 60,61 , strong adhesion receptor activation [153][154][155] , presence of monosodium urate (MSU) 88 , or phorbol-myristate-acetate (PMA) stimulation 2,12 , results in an excess of reactive oxygen species (ROS), leading to neutrophil cytolysis. Similarly, excessive increases in intracellular calcium [Ca 2+ ] i by ionomycin results in non-apoptotic neutrophil death 12,81 .…”

Section: Nets and Eets In Bacterial Infectionsmentioning

confidence: 99%

In vivo evidence for extracellular DNA trap formation

et al. 2020

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Extracellular DNA trap formation is a cellular function of neutrophils, eosinophils, and basophils that facilitates the immobilization and killing of invading microorganisms in the extracellular milieu. To form extracellular traps, granulocytes release a scaffold consisting of mitochondrial DNA in association with granule proteins. As we understand more about the molecular mechanism for the formation of extracellular DNA traps, the in vivo function of this phenomenon under pathological conditions remains an enigma. In this article, we critically review the literature to summarize the evidence for extracellular DNA trap formation under in vivo conditions. Extracellular DNA traps have not only been detected in infectious diseases but also in chronic inflammatory diseases, as well as in cancer. While on the one hand, extracellular DNA traps clearly exhibit an important function in host defense, it appears that they can also contribute to the maintenance of inflammation and metastasis, suggesting that they may represent an interesting drug target for such pathological conditions. Facts •The demonstration of extracellular DNA traps in vivo requires sections of affected tissues, which are to be investigated with special staining techniques. These structures are seen in multiple inflammatory and cancer diseases.Is there a simple biomarker that reflects extracellular DNA trap formation?• What is the contribution of extracellular microbe killing compared to intracellular killing following phagocytosis?• The mechanism of DNA trap formation is unknown.

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Section: Nets and Eets In Bacterial Infectionsmentioning

confidence: 99%

In vivo evidence for extracellular DNA trap formation

et al. 2020

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“…). PMD occurs in the absence of granule fusions and retains the delimiting membranes of specific granules, which appear as emptying containers and; (iii) Cytolysis: granule deposition in tissues after cell death, and that may be associated or not with DNA‐formed EETs . FEGs remain ligand‐responsive and competent to secrete and, for this reason, are considered functionally active …”

Section: Eosinophil Activation Triggers Structural Changes Of Specifimentioning

confidence: 99%

“…70 Cytolysis: granule deposition in tissues after cell death, and that may be associated or not with DNA-formed EETs. 13,14,75 FEGs remain ligand-responsive and competent to secrete and, for this reason, are considered functionally active. 13,52 Exocytosis is an uncommon in vivo eosinophil degranulation event, but can be observed during in vitro interaction of eosinophils with different parasitic helminths 72 and environmental fungi 73 or after in vitro stimulation with high concentration of TNF-.…”

Section: Eosinophil Specific Granules Are Membranous Compartmentalizementioning

confidence: 99%

Contemporary understanding of the secretory granules in human eosinophils

Melo

Weller²

2018

Journal of Leukocyte Biology

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Eosinophil secretory (specific) granules have a unique morphology and are both a morphologic hallmark of eosinophils and fundamental to eosinophil-mediated responses. Eosinophil mediators with multiple functional activities are presynthesized and stored within these granules, poised for very rapid, stimulus-induced secretion. The structural organization and changes of eosinophil specific granules are revealing in demonstrating the complex and diverse secretory activities of this cell. Here, we review our current knowledge on the architecture, composition, and function of eosinophil specific granules as highly elaborated organelles able to produce vesiculotubular carriers and to interplay with the intracellular vesicular trafficking. We reconsider prior identifications of eosinophil cytoplasmic granules, including "primary," "secondary," "microgranules," and "small granules"; and consonant with advances, we provide a contemporary recognition that human eosinophils contain a single population of specific granules and their developmental precursors and derived secretory vesicles.

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“…The release, or not, of toxic or pro-inflammatory intracellular materials in vivo is closely linked to the mechanism associated with eosinophil death (either apoptosis or necrosis or necroptosis). Apoptotic eosinophils are phagocytosed by macrophages and epithelial cells that digest eosinophil contents, while necrotic and necroptotic 68 eosinophils lose membrane integrity and consequently release granules and mediators leading to tissue damage and inflammation. Importantly, eosinophil adhesion via interaction of its integrins (particularly αMβ2) with appropriate ligands is a required step for eosinophil degranulation.…”

Section: Commonalities and Differences Among Il-3 Il-5 And Gm-cmentioning

confidence: 99%

Essential mechanisms of differential activation of eosinophils by IL-3 compared to GM-CSF and IL-5

Esnault

Kelly

2017

Crit Rev Immunol

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There is compelling evidence that the eosinophils bring negative biological outcomes in several diseases, including eosinophilic asthma and hypereosinophilic syndromes. Eosinophils produce and store a broad range of toxic proteins and other mediators that enhance the inflammatory response and lead to tissue damage. For instance, in asthma, there is a close relationship between increased lung eosinophilia, asthma exacerbation, and loss of lung function. The use of an anti-IL-5 therapy in severe eosinophilic asthmatic patients is efficient to reduce exacerbations. However, anti-IL-5-treated patients still display a relatively high amount of functional lung tissue eosinophils, indicating that supplemental therapies are required to damper the eosinophil functions. Our recent published works, suggest that compared to IL-5, IL-3 can more strongly and differentially affect eosinophil functions. In this review, we will summarize our and other investigations that have compared the effects of the three β-chain receptor cytokines (IL-5, GM-CSF and IL-3) on eosinophil biology. We will focus on how IL-3 differentially activates eosinophils compared to IL-5 or GM-CSF.

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Adhesion-induced eosinophil cytolysis requires the receptor-interacting protein kinase 3 (RIPK3)–mixed lineage kinase-like (MLKL) signaling pathway, which is counterregulated by autophagy

Abstract: We report that adhesion-induced eosinophil cytolysis takes place through RIPK3-MLKL-dependent necroptosis, which can be counterregulated by autophagy.

Cited by 55 publications

References 51 publications

In vivo evidence for extracellular DNA trap formation

In vivo evidence for extracellular DNA trap formation

Contemporary understanding of the secretory granules in human eosinophils

Essential mechanisms of differential activation of eosinophils by IL-3 compared to GM-CSF and IL-5

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