Neutrophil granules: a library of innate immunity proteins

Borregaard, Niels; Sørensen, Ole E.; Theilgaard‐Mönch, Kim

doi:10.1016/j.it.2007.06.002

Cited by 611 publications

(599 citation statements)

References 51 publications

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“…Within neutrophils, TRAIL protein is reported to be detectable in all types of granules, but it is especially abundant in azurophil granules and secretory vesicles (8,50). We demonstrated clearly that MV-Vac infection per se was associated with granule release from neutrophils.…”

Section: Discussionmentioning

confidence: 60%

Attenuated, Oncolytic, but Not Wild-Type Measles Virus Infection Has Pleiotropic Effects on Human Neutrophil Function

Zhang

Patel

Dey

et al. 2012

The Journal of Immunology

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We previously showed that neutrophils play a role in regression of human tumor xenografts in immunodeficient mice following oncolytic vaccine measles virus (MV-Vac) treatment. In this study, we sought, using normal human neutrophils, to identify potential neutrophil-mediated mechanisms for the attenuated MV-Vac induced effects seen in vivo, by comparison with those consequent on wild-type (WT-MV) infection. Both MV-Vac and WT-MV infected and replicated within neutrophils, despite lack of SLAM expression. In both cases, neutrophils survived longer ex vivo postinfection. Furthermore, MV-Vac (but not WT-MV) infection activated neutrophils and stimulated secretion of several specific antitumor cytokines (IL-8, TNF-α, MCP-1, and IFN-α) via induction of de novo RNA and protein synthesis. In addition, MV-Vac (but not WT-MV) infection caused TRAIL secretion in the absence of de novo synthesis by triggering release of prefabricated TRAIL, via a direct effect upon degranulation. The differences between the outcome of infection by MV-Vac and WT-MV were not entirely explained by differential infection and replication of the viruses within neutrophils. To our knowledge, this is the first demonstration of potential mechanisms of oncolytic activity of an attenuated MV as compared with its WT parent. Furthermore, our study suggests that neutrophils have an important role to play in the antitumor effects of oncolytic MV.

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Section: Discussionmentioning

confidence: 60%

Attenuated, Oncolytic, but Not Wild-Type Measles Virus Infection Has Pleiotropic Effects on Human Neutrophil Function

Zhang

Patel

Dey

et al. 2012

The Journal of Immunology

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“…Determination of the gene expression profile of neutrophils from the bone marrow, circulating blood or a skin lesion of mice indicated that transmigration through the vessel wall initiates a new transcription program leading to the synthesis of regulatory and cell-fate determining proteins [11,105,106]. Phagocytosis of opsonized particles via Fc and/or complement receptors also altered the expression of numerous genes, many of them affecting proteins involved in apoptotic pathways [56,57].…”

Section: Protein Synthesismentioning

confidence: 99%

“…Neutrophils possess 4 different types of granules that develop in different stages of maturation in the bone marrow [11]. The contents of these granules are regarded as specific neutrophil proteins involved in killing and degradation of phagocytosed pathogens.…”

Section: Additional Functions Of Granule Proteinsmentioning

confidence: 99%

“…Some of the hydrolases were shown to degrade extracellular (tissue factor pathway inhibitor, TFPI) or intracellular (insulin receptor substrate-1, IRS-1) proteins and influence thereby coagulation and insulin resistance, resp. Selected neutrophil granule proteins are also expressed upon stimulation of endothelial or epithelial cells [11].…”

Section: Additional Functions Of Granule Proteinsmentioning

confidence: 99%

“…Killing and degradation of the microorganism proceed in the small phagosomal space in a concentrated action of the involved ingredients, although the contribution of the individual factors may vary depending on the type of microorganism [89,91]. The molecular details of these processes have been worked out and summarized in recent excellent reviews [11,58,66,75,77,78,80,102,115].…”

Section: Introductionmentioning

confidence: 99%

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Changing world of neutrophils

Tímár

Lörincz

Ligeti

2013

Pflugers Arch - Eur J Physiol

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Identification of small‐molecule elastase inhibitors as antagonists of IL‐36 cytokine activation

et al. 2018

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IL‐1 family cytokines act as apical initiators of inflammation in many settings and can promote the production of a battery of inflammatory cytokines, chemokines and other inflammatory mediators in diverse cell types. IL‐36α, IL‐36β and IL‐36γ, which belong to the extended IL‐1 family, have been implicated as key initiators of skin inflammation in psoriasis. IL‐36γ is highly upregulated in lesional skin from psoriatic individuals, and heritable mutations in the natural IL‐36 receptor antagonist result in a severe form of psoriasis. IL‐36 family cytokines are initially expressed as inactive precursors that require proteolytic processing for activation. The neutrophil granule‐derived protease elastase proteolytically processes and activates IL‐36α and IL‐36γ, increasing their biological activity ~ 500‐fold, and also robustly activates IL‐1α and IL‐33 through limited proteolytic processing. Consequently, inhibitors of elastase activity may have potential as anti‐inflammatory agents through antagonizing the activation of multiple IL‐1 family cytokines. Using in silico screening approaches, we have identified small‐molecule inhibitors of elastase that can antagonize activation of IL‐36γ by the latter protease. The compounds reported herein may have utility as lead compounds for the development of inhibitors of elastase‐mediated activation of IL‐36 and other IL‐1 family cytokines in inflammatory conditions, such as psoriasis.

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Neutrophil granules: a library of innate immunity proteins

Cited by 611 publications

References 51 publications

Attenuated, Oncolytic, but Not Wild-Type Measles Virus Infection Has Pleiotropic Effects on Human Neutrophil Function

Attenuated, Oncolytic, but Not Wild-Type Measles Virus Infection Has Pleiotropic Effects on Human Neutrophil Function

Changing world of neutrophils

Identification of small‐molecule elastase inhibitors as antagonists of IL‐36 cytokine activation

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