Myeloperoxidase Stimulates Neutrophil Degranulation

Grigorieva, Daria V.; Gorudko, Irina V.; Sokolov, A. V.; Kostevich, Valeria A.; Vasilyev, V. B.; Sn, Cherenkevich; Панасенко, О. М.

doi:10.1007/s10517-016-3446-7

Cited by 33 publications

(27 citation statements)

References 12 publications

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“…Some evidences suggest that the pyroptosis of neutrophils is an important way for neutrophils to function during sepsis and that neutrophils continuously synthesize and secrete IL-1β and IL-18 during pyroptosis. Eventually, neutrophils swell slightly and develop a membrane lysis, producing cytoplasmic DAMP (damage-associated molecular patterns) [10] and releasing a large number of immunomodulatory cytokines such as IL-10, IL-13, chemokines such as IL-8, MIP-1α, and myeloperoxidase (MPO), cathepsin G and other granzymes [31]. After the neutrophil membrane lysis, intracellular pathogens form a pore-induced intracellar trap (PIT) though they have not been released directly extracellularly.…”

Section: Introductionmentioning

confidence: 99%

Neutrophil pyroptosis: new perspectives on sepsis

Liu

Sun

2019

Cell. Mol. Life Sci.

147

104

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Pyroptosis is a caspase-1 or caspase-4/5/11-dependent programmed cell death associated with inflammation, which is initiated by inflammasomes or cytosolic LPS in innate immunity. Sepsis is a life-threatening organ dysfunction caused by an imbalance in the body's response to infection. It is a complex interaction between the pathogen and the host's immune system. Neutrophils play the role of a double-edged sword in sepsis, and a number of studies have previously shown that regulation of neutrophils is the most crucial part of sepsis treatment. Pyroptosis is one of the important forms for neutrophils to function, which is increasingly understood as a host active immune response. There is ample evidence that neutrophil pyroptosis may play an important role in sepsis. In recent years, a breakthrough in pyroptosis research has revealed the main mechanism of pyroptosis. However, the potential value of neutrophil pyroptosis in the treatment of sepsis did not draw enough attention. A literature review was performed on the main mechanism of pyroptosis in sepsis and the potential value of neutrophils pyroptosis in sepsis, which may be suitable targets for sepsis treatment in future.

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Section: Introductionmentioning

confidence: 99%

Neutrophil pyroptosis: new perspectives on sepsis

Liu

Sun

2019

Cell. Mol. Life Sci.

147

104

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“…The potent HNE can be inhibited at the site of inflammation by endogenous serine protease inhibitors (serpins) including ␣1-antitrypsin (A1AT), an abundant plasma N-glycoprotein produced by hepatocytes (20). HNE may be released from neutrophils upon stimuli-induced activation by lipopolysaccharide (LPS) or N-formylmethionine-leucyl-phenylalanine (fMLP) (21,22). In the extracellular environment, HNE serves multiple protective and regulatory roles within the innate immune system.…”

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confidence: 99%

Paucimannose-Rich N-glycosylation of Spatiotemporally Regulated Human Neutrophil Elastase Modulates Its Immune Functions*.

Loke

Østergaard

Heegaard

et al. 2017

Molecular & Cellular Proteomics

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Human neutrophil elastase (HNE) is an important -glycosylated serine protease in the innate immune system, but the structure and immune-modulating functions of HNE-glycosylation remain undescribed. Herein, LC-MS/MS-based glycan, glycopeptide and glycoprotein profiling were utilized to first determine the heterogeneous -glycosylation of HNE purified from neutrophil lysates and then from isolated neutrophil granules of healthy individuals. The spatiotemporal expression of HNE during neutrophil activation and the biological importance of its-glycosylation were also investigated using immunoblotting, cell surface capture, native MS, receptor interaction, protease inhibition, and bacteria growth assays. Site-specific HNE glycoprofiling demonstrated that unusual paucimannosidic -glycans, particularly Manα1,6Manβ1,4GlcNAcβ1,4(Fucα1,6)GlcNAcβ, predominantly occupied Asn124 and Asn173. The equally unusual core fucosylated monoantenna complex-type-sialoglycans also decorated these two fully occupied sites. In contrast, the mostly unoccupied Asn88 carried nonfucosylated paucimannosidic -glycans probably resulting from low glycosylation site solvent accessibility. Asn185 was not glycosylated. Subcellular- and site-specific glycoprofiling showed highly uniform-glycosylation of HNE residing in distinct neutrophil compartments. Stimulation-induced cell surface mobilization demonstrated a spatiotemporal regulation, but not cell surface-specific glycosylation signatures, of HNE in activated human neutrophils. The three glycosylation sites of HNE were located distal to the active site indicating glycan functions other than interference with HNE enzyme activity. Functionally, the paucimannosidic HNE glycoforms displayed preferential binding to human mannose binding lectin compared with the HNE sialoglycoforms, suggesting a glycoform-dependent involvement of HNE in complement activation. The heavily -glycosylated HNE protease inhibitor, α1-antitrypsin, displayed concentration-dependent complex formation and preferred glycoform-glycoform interactions with HNE. Finally, both enzymatically active HNE and isolated HNE-glycans demonstrated low micromolar concentration-dependent growth inhibition of clinically-relevant , suggesting some bacteriostatic activity is conferred by the HNE-glycans. Taken together, these observations support that the unusual HNE -glycosylation, here reported for the first time, is involved in modulating multiple immune functions central to inflammation and infection.

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“…As a result of cellular necrosis several local changes may result in tissue damage including release of mtDNA, which in turn activates TLR9 and may promote further release of ROS and tissue damage. ROS is essential for multiple homeostatic cellular functions, but uncontrolled activity results in cell injury during infections, or sterile injury by triggering NET formation, induction of NF‐κB transcription and possibly autophagy. Although ROS activity and lysosome acidification are important for TLR9 signaling in macrophages, the impact of these factors in neutrophils is less certain.…”

Section: Discussionmentioning

confidence: 99%

Endotracheal intubation results in acute tracheal damage induced by mtDNA/TLR9/NF-κB activity

Puyo

Earhart

Staten

et al. 2018

Journal of Leukocyte Biology

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Tracheitis secondary to placement of an endotracheal tube (ETT) is characterized by neutrophil accumulation in the tracheal lumen, which is generally associated with epithelial damage. Mitochondrial DNA (mtDNA), has been implicated in systemic inflammation and organ dysfunction following trauma; however, less is known about the effects of a foreign body on local trauma and tissue damage. We hypothesized that tracheal damage secondary to the ETT will result in local release of mtDNA at sufficient levels to induce TLR9 and NF‐κB activation. In a swine model we compared the differences between uncoated, and chloroquine (CQ) and N‐acetylcysteine (NAC) coated ETTs as measured by tracheal lavage fluids (TLF) over a period of 6 h. The swine model allowed us to recreate human conditions. ETT presence was characterized by neutrophil activation, necrosis, and release of proinflammatory cytokines mediated by TLR9/NF‐κB induction. Amelioration of the tracheal damage was observed in the CQ and NAC coated ETT group as shown in tracheal tissue specimens and TLF. The role of TLR9/NF‐κB dependent activity was confirmed by HEK‐Blue hTLR9 reporter cell line analysis after coincubation with TLF specimens with predetermined concentrations of NAC or CQ alone or TLR9 inhibitory oligodeoxynucleotide (iODN). These findings indicate that therapeutic interventions aimed at preventing mtDNA/TLR9/NF‐κB activity may have benefits in prevention of acute tracheal damage.

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Myeloperoxidase Stimulates Neutrophil Degranulation

Cited by 33 publications

References 12 publications

Neutrophil pyroptosis: new perspectives on sepsis

Neutrophil pyroptosis: new perspectives on sepsis

Paucimannose-Rich N-glycosylation of Spatiotemporally Regulated Human Neutrophil Elastase Modulates Its Immune Functions*.

Endotracheal intubation results in acute tracheal damage induced by mtDNA/TLR9/NF-κB activity

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