Myeloperoxidase negatively regulates the expression of proinflammatory cytokines and chemokines by zymosan-induced mouse neutrophils

Endo, Daiki; Saito, Takayuki; Umeki, Yu; Suzuki, Kazuo; Aratani, Yasuaki

doi:10.1007/s00011-015-0899-5

Cited by 21 publications

(13 citation statements)

References 42 publications

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Section: Influence Of Mpo On Cytokine Production During Lung Inflamentioning

confidence: 75%

“…Mpo − / − peritoneal cavity neutrophils stimulated in vitro with the toll-like receptor (TLR) 2 agonist zymosan, had increased production of proinflammatory MIP-1α, MIP-1β, IL-1α, IL-1β, and TNF-α as compared to WT [72]. This finding correlated to in vivo findings as indicated by a similar increase in the same cytokines in Mpo − / − mice following zymosan administration [72]. Similarly, it was found that Mpo − / − mice with zymosan-induced lung inflammation exhibited elevated levels of MIP-2, which correlated with increased number of neutrophils in the lung [73].…”

Section: Influence Of Mpo On Cytokine Production During Lung Inflamentioning

confidence: 99%

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Myeloperoxidase: A new player in autoimmunity

Strzępa

Pritchard

Dittel

2017

Cellular Immunology

182

103

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Myeloperoxidase (MPO) is the most toxic enzyme found in the azurophilic granules of neutrophils. MPO utilizes H2O2 to generate hypochlorous acid (HClO) and other reactive moieties, which kill pathogens during infections. In contrast, in the setting of sterile inflammation, MPO and MPO-derived oxidants are thought to be pathogenic, promoting inflammation and causing tissue damage. In contrast, evidence also exists that MPO can limit the extent of immune responses. Elevated MPO levels and activity are observed in a number of autoimmune diseases including in the central nervous system (CNS) of multiple sclerosis (MS) and the joints of rheumatoid arthritis (RA) patients. A pathogenic role for MPO in driving autoimmune inflammation was demonstrated using mouse models. Mechanisms whereby MPO is thought to contribute to disease pathogenesis include tuning of adaptive immune responses and/or the induction of vascular permeability.

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Section: Influence Of Mpo On Cytokine Production During Lung Inflamentioning

confidence: 75%

Section: Influence Of Mpo On Cytokine Production During Lung Inflamentioning

confidence: 99%

Myeloperoxidase: A new player in autoimmunity

Strzępa

Pritchard

Dittel

2017

Cellular Immunology

182

103

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“…Previous studies have reported similar or altered neutrophil tissue infiltration for MPOdeficient mice in various disease models[38][39][40][41][42][43][44][45] which could affect oxidative stress levels. However, in the typhoid fever model neutrophil recruitment as detected by an antibody to Ly-6G was similar in infected wild-type and MPO-deficient mice(Fig.…”

mentioning

confidence: 99%

Myeloperoxidase targets oxidative host attacks to Salmonella and prevents collateral tissue damage

et al. 2017

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Host control of infections crucially depends on the capability to kill pathogens with reactive oxygen species (ROS). However, these toxic molecules can also readily damage host components and cause severe immunopathology. Here, we show that neutrophils use their most abundant granule protein, myeloperoxidase, to target ROS specifically to pathogens while minimizing collateral tissue damage. A computational model predicted that myeloperoxidase efficiently scavenges diffusible HO at the surface of phagosomal Salmonella and converts it into highly reactive HOCl (bleach), which rapidly damages biomolecules within a radius of less than 0.1 μm. Myeloperoxidase-deficient neutrophils were predicted to accumulate large quantities of HO that still effectively kill Salmonella, but most HO would leak from the phagosome. Salmonella stimulation of neutrophils from normal and myeloperoxidase-deficient human donors experimentally confirmed an inverse relationship between myeloperoxidase activity and extracellular HO release. Myeloperoxidase-deficient mice infected with Salmonella had elevated hydrogen peroxide tissue levels and exacerbated oxidative damage of host lipids and DNA, despite almost normal Salmonella control. These data show that myeloperoxidase has a major function in mitigating collateral tissue damage during antimicrobial oxidative bursts, by converting diffusible long-lived HO into highly reactive, microbicidal and locally confined HOCl at pathogen surfaces.

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“…Upon encountering the host immune cells, Aspergillus induced neutrophil degranulation, from which MPO had the capacity to attenuate TNF‐α. Indeed, MPO deficiency in mice had been reported to exacerbate inflammation and pneumonia with concurrent increased pro‐inflammatory cytokine levels (Endo, Saito, Umeki, Suzuki, & Aratani, ; Homme, Tateno, Miura, Ohno, & Aratani, ). On the other hand, the modulation of IL‐1β was dependent on cellular contact through the involvement of CR3.…”

Section: Discussionmentioning

confidence: 87%

Neutrophils differentially attenuate immune response toAspergillusinfection through complement receptor 3 and induction of myeloperoxidase

Goh

Ravikumar

Win

et al. 2017

Cellular Microbiology

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Invasive aspergillosis (IA) remains a major cause of morbidity in immunocompromised hosts. This is due to the inability of the host immunity to respond appropriately to Aspergillus. An established risk factor for IA is neutropenia that is encountered by patients undergoing chemotherapy. Herein, we investigate the role of neutrophils in modulating host response to Aspergillus. We found that neutrophils had the propensity to suppress proinflammatory cytokine production but through different mechanisms for specific cytokines. Cellular contact was requisite for the modulation of interleukin-1 beta production by Aspergillus with the involvement of complement receptor 3. On the other hand, inhibition of tumour necrosis factor-alpha production (TNF-α) was cell contact-independent and mediated by secreted myeloperoxidase. Specifically, the inhibition of TNF-α by myeloperoxidase was through the TLR4 pathway and involved interference with the mRNA transcription of TNF receptor-associated factor 6/interferon regulatory factor 5. Our study illustrates the extended immune modulatory role of neutrophils beyond its primary phagocytic function. The absence of neutrophils and loss of its inhibitory effect on cytokine production explains the hypercytokinemia seen in neutropenic patients when infected with Aspergillus.

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Myeloperoxidase negatively regulates the expression of proinflammatory cytokines and chemokines by zymosan-induced mouse neutrophils

Abstract: MPO deficiency upregulates the expression of several proinflammatory cytokines and chemokines in mouse neutrophils.

Cited by 21 publications

References 42 publications

Myeloperoxidase: A new player in autoimmunity

Myeloperoxidase: A new player in autoimmunity

Myeloperoxidase targets oxidative host attacks to Salmonella and prevents collateral tissue damage

Neutrophils differentially attenuate immune response toAspergillusinfection through complement receptor 3 and induction of myeloperoxidase

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