Effect of glycine on the release of reactive oxygen species in human neutrophils

Giambelluca, Miriam S.; Gende, Oscar A.

doi:10.1016/j.intimp.2008.09.006

Cited by 11 publications

(8 citation statements)

References 27 publications

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“…Their results cannot be directly compared with our results, because of differences in species (rat versus human) with the possible difference in the compositions of GlyR subtypes (35), preparation methods for neutrophils (exudates cells from glycogen-induced peritonitis versus neutrophils purified from venous blood), and stimuli (LPS or fMLP to resting neutrophils versus LPC in the presence of glycine to E. coli-ingested neutrophils). It was recently reported that fMLP-induced [Ca +2 ] i increase in human neutrophils is potentiated by glycine (59 (53,54), and is involved in oxidant stress-induced cell death (53,(71)(72)(73) and chemokine production (74). Therefore, TRPM2 is an important target for the development of therapeutic strategies against oxidative stress-related disorders (for review, see Ref.…”

Section: Discussionmentioning

confidence: 99%

Lysophosphatidylcholine Increases Neutrophil Bactericidal Activity by Enhancement of Azurophil Granule-Phagosome Fusion via Glycine·GlyRα2/TRPM2/p38 MAPK Signaling

Hong¹,

Kim²,

Ham³

et al. 2010

The Journal of Immunology

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Section: Discussionmentioning

confidence: 99%

Lysophosphatidylcholine Increases Neutrophil Bactericidal Activity by Enhancement of Azurophil Granule-Phagosome Fusion via Glycine·GlyRα2/TRPM2/p38 MAPK Signaling

Hong¹,

Kim²,

Ham³

et al. 2010

The Journal of Immunology

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“…we found that serine racemase is present on the neutrophil cell surface and release of d -serine increases in response to PMA challenge. These data suggest that d -serine acts as a co-agonist recruited to maintain NMDAR activity in neutrophils, rather than glycine which inhibits the neutrophil respiratory burst [62]. Thus, the necessary machinery is in place in human neutrophils for glutamate generated via glutaminase to activate NMDAR in an auto- and paracrine manner.…”

Section: Discussionmentioning

confidence: 99%

NMDA receptor modulation of glutamate release in activated neutrophils

et al. 2019

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BackgroundNeutrophil depletion improves neurologic outcomes in experimental sepsis/brain injury. We hypothesized that neutrophils may exacerbate neuronal injury through the release of neurotoxic quantities of the neurotransmitter glutamate.MethodsReal-time glutamate release by primary human neutrophils was determined using enzymatic biosensors. Bacterial and direct protein-kinase C (Phorbol 12-myristate 13-acetate; PMA) activation of neutrophils in human whole blood, isolated neutrophils or human cell lines were compared in the presence/absence of N-Methyl-d-aspartic acid receptor (NMDAR) antagonists. Bacterial and direct activation of neutrophils from wild-type and transgenic murine neutrophils deficient in NMDAR-scaffolding proteins were compared using flow cytometry (phagocytosis, reactive oxygen species (ROS) generation) and real-time respirometry (oxygen consumption).FindingsBoth glutamate and the NMDAR co-agonist d-serine are rapidly released by neutrophils in response to bacterial and PMA-induced activation. Pharmacological NMDAR blockade reduced both the autocrine release of glutamate, d-serine and the respiratory burst by activated primary human neutrophils. A highly specific small-molecule inhibitor ZL006 that limits NMDAR-mediated neuronal injury also reduced ROS by activated neutrophils in a murine model of peritonitis, via uncoupling of the NMDAR GluN2B subunit from its' scaffolding protein, postsynaptic density protein-95 (PSD-95). Genetic ablation of PSD-95 reduced ROS production by activated murine neutrophils. Pharmacological blockade of the NMDAR GluN2B subunit reduced primary human neutrophil activation induced by Pseudomonas fluorescens, a glutamate-secreting Gram-negative bacillus closely related to pathogens that cause hospital-acquired infections.InterpretationThese data suggest that release of glutamate by activated neutrophils augments ROS production in an autocrine manner via actions on NMDAR expressed by these cells.FundGLA: Academy Medical Sciences/Health Foundation Clinician Scientist. AVG is a Wellcome Trust Senior Research Fellow.

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“…Glycine similarly modulated peritoneal macrophage function via its uptake by neutral amino acid transporters in peritoneal macrophages even though those cells expressed the GlyR α 1 subunit and gephyrin [59]. In addition to the effects of glycine on neutrophils that were apparently mediated by strychnine-sensitive signaling, it has also been reported that both N-formyl methionyl leucyl phenylalanine peptide and phorbol myristate acetate-induced reactive oxygen species production in neutrophils can be inhibited by glycine with EC50s of 0.5 – 1.5 mM by a strychnine-insensitive mechanism that is unrelated to changes of Ca f [165]. None of the studies of inflammatory cells displaying immunomodulatory effects of glycine and implicating GlyR in them extended the models to assess glycine modulation of necrosis in those cells, which would clearly be of interest in view of the work that has shown strong protection by glycine against pyroptosis of macrophages [50–54,91,92].…”

Section: Relationship Of Cytoprotection To Neuronal Glycine Receptorsmentioning

confidence: 99%

“…Infusion of glycine at the end of 6 hours of skeletal muscle ischemia and then during the first hour of reperfusion decreased necrosis and increased metabolic and functional recovery [242]. Glycine suppression of reactive oxygen species production by neutrophils [165] may have played a major role in this skeletal muscle effect [243]. …”

Section: Glycine Effects On Disease Models In Vivomentioning

confidence: 99%

The role of glycine in regulated cell death

Weinberg

Bienholz

Venkatachalam

2016

Cell. Mol. Life Sci.

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The cytoprotective effects of glycine against cell death have been recognized for over 28 years. They are expressed in multiple cell types and injury settings that lead to necrosis, but are still not widely appreciated or considered in the conceptualization of cell death pathways. In this paper we review the available data on the expression of this phenomenon, its relationship to major pathophysiologic pathways that lead to cell death and immunomodulatory effects, the hypothesis that it involves suppression by glycine of the development of a hydrophilic death channel of molecular dimensions in the plasma membrane, and evidence for its impact on disease processes in vivo.

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Effect of glycine on the release of reactive oxygen species in human neutrophils

Cited by 11 publications

References 27 publications

Lysophosphatidylcholine Increases Neutrophil Bactericidal Activity by Enhancement of Azurophil Granule-Phagosome Fusion via Glycine·GlyRα2/TRPM2/p38 MAPK Signaling

Lysophosphatidylcholine Increases Neutrophil Bactericidal Activity by Enhancement of Azurophil Granule-Phagosome Fusion via Glycine·GlyRα2/TRPM2/p38 MAPK Signaling

NMDA receptor modulation of glutamate release in activated neutrophils

The role of glycine in regulated cell death

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