Involvement of NO in the failure of neutrophil migration in sepsis induced by <i>Staphylococcus aureus</i>

Crosara-Alberto, Daniella P.; Darini, Ana Lúcia da Costa; Inoue, Rosana Yuri; Silva, João; Ferreira, Sérgio Henrique; Cunha, Fernando Q.

doi:10.1038/sj.bjp.0704734

Cited by 66 publications

(72 citation statements)

References 70 publications

(75 reference statements)

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“…We showed that the failure of neutrophil migration is observed in severe polymicrobial sepsis (5,7,12), Gram negative or positive (6,8). The impairment of neutrophil migration was associated with a decrease in the rolling and adhesion of neutrophils on endothelial cells, leading to a failure of bacterial clearance in the infection focus, increased number of bacteria in blood, high levels of circulating cytokines/chemokines, and mortality.…”

Section: Il-17 Receptor Signaling Is Required To Controlmentioning

confidence: 92%

“…These cells are ideally suited to the elimination of pathogenic bacteria due to their capability of phagocytosis, releasing the stores of granular lytic enzymes and antimicrobial polypeptides into the phagolysosome (1). In this way, migrating neutrophils may control bacterial growth and, consequently, prevent bacterial dissemination and death (2)(3)(4)(5)(6)(7)(8). However, once the host fails to restrict the pathogens to a localized area, they and/or their products may spread systemically, resulting in an overproduction of cytokines/chemokines, systemic inflammatory response syndrome, septic shock, and death (9 -11).…”

Section: Il-17 Receptor Signaling Is Required To Controlmentioning

confidence: 99%

“…The impairment of neutrophil migration was associated with a decrease in the rolling and adhesion of neutrophils on endothelial cells, leading to a failure of bacterial clearance in the infection focus, increased number of bacteria in blood, high levels of circulating cytokines/chemokines, and mortality. Conversely, in mice subjected to non-severe sepsis, in which neutrophil migration failure was not observed, bacterial infection was restricted to the peritoneal cavity and, consequently, no mortality was observed (5)(6)(7)(8)12). Furthermore, neutrophils obtained from septic patients showed reduced chemotaxis in response to IL-8, leukotriene B 4 , and fMLP, and the intensity of the reduction of neutrophil chemotaxis correlated with the severity of the sepsis (13,14).…”

Section: Il-17 Receptor Signaling Is Required To Controlmentioning

confidence: 99%

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IL-17 Receptor Signaling Is Required to Control Polymicrobial Sepsis

Freitas

Alves‐Filho

Victoni

et al. 2009

The Journal of Immunology

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Sepsis is a systemic inflammatory response resulting from the inability of the host to contain the infection locally. Previously, we demonstrated that during severe sepsis there is a marked failure of neutrophil migration to the infection site, which contributes to dissemination of infection, resulting in high mortality. IL-17 plays an important role in neutrophil recruitment. Herein, we investigated the role of IL-17R signaling in polymicrobial sepsis induced by cecal ligation and puncture (CLP). It was observed that IL-17R-deficient mice, subjected to CLP-induced non-severe sepsis, show reduced neutrophil recruitment into the peritoneal cavity, spread of infection, and increased systemic inflammatory response as compared with C57BL/6 littermates. As a consequence, the mice showed an increased mortality rate. The ability of IL-17 to induce neutrophil migration was demonstrated in vivo and in vitro. Beside its role in neutrophil recruitment to the infection focus, IL-17 enhanced the microbicidal activity of the migrating neutrophils by a mechanism dependent on NO. Therefore, IL-17 plays a critical role in host protection during polymicrobial sepsis.

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Section: Il-17 Receptor Signaling Is Required To Controlmentioning

confidence: 92%

Section: Il-17 Receptor Signaling Is Required To Controlmentioning

confidence: 99%

Section: Il-17 Receptor Signaling Is Required To Controlmentioning

confidence: 99%

See 1 more Smart Citation

IL-17 Receptor Signaling Is Required to Control Polymicrobial Sepsis

Freitas

Alves‐Filho

Victoni

et al. 2009

The Journal of Immunology

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“…In addition, neutrophils also release cytokines and chemokines, which enhance their own recruitment and activation as well as inducing the migration of other immune cells (2). Our previous studies showed that lethal sepsis induced by cecal ligation and puncture (CLP) 3 or Staphylococcus aureus inoculation is associated with reduction of neutrophil rolling, adhesion, and transmigration to sites of infection (3)(4)(5)(6)(7)(8). The impairment of neutrophil migration was also associated with high mortality and increased numbers of bacteria in peritoneal exudates and blood.…”

mentioning

confidence: 99%

“…The impairment of neutrophil migration was also associated with high mortality and increased numbers of bacteria in peritoneal exudates and blood. Conversely, in nonlethal sepsis, the bacterial infection was restricted to the peritoneal cavity, and neutrophil rolling, adhesion, and migration were not affected, and no significant mortality was observed (3)(4)(5)(6)(7)(8). The mechanism involved in the paralysis of neutrophil migration function is still elusive.…”

mentioning

confidence: 99%

IL-12, but Not IL-18, Is Critical to Neutrophil Activation and Resistance to Polymicrobial Sepsis Induced by Cecal Ligation and Puncture

Moreno¹,

Alves‐Filho²,

Alfaya³

et al. 2006

The Journal of Immunology

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Sepsis is a systemic inflammatory response resulting from local infection due, at least in part, to impaired neutrophil migration. IL-12 and IL-18 play an important role in neutrophil migration. We have investigated the mechanism and relative role of IL-12 and IL-18 in polymicrobial sepsis induced by cecal ligation and puncture (CLP) in mice. Wild-type (WT) and IL-18−/− mice were resistant to sublethal CLP (SL-CLP) sepsis. In contrast, IL-12−/− mice were susceptible to SL-CLP sepsis with high bacteria load in peritoneal cavity and systemic inflammation (serum TNF-α and lung neutrophil infiltration). The magnitude of these events was similar to those observed in WT mice with lethal CLP sepsis. The inability of IL-12−/− mice to restrict the infection was not due to impairment of neutrophil migration, but correlated with decrease of phagocytosis, NO production, and microbicidal activities of their neutrophils, and with reduction of systemic IFN-γ synthesis. Consistent with this observation, IFN-γ−/− mice were as susceptible to SL-CLP as IL-12−/− mice. Moreover, addition of IFN-γ to cultures of neutrophils from IL-12−/− mice restored their phagocytic, microbicidal activities and NO production. Mortality of IL-12−/− mice to SL-CLP was prevented by treatment with IFN-γ. Thus we show that IL-12, but not IL-18, is critical to an efficient host defense in polymicrobial sepsis. IL-12 acts through induction of IFN-γ and stimulation of phagocytic and microbicidal activities of neutrophils, rather than neutrophil migration per se. Our data therefore provide further insight into the defense mechanism against this critical area of infectious disease.

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Inducible nitric oxide synthase: An asset to neutrophils

Saini

Singh

2018

Journal of Leukocyte Biology

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Neutrophils play a key role in innate immune responses against foreign intrusion and influence the subsequent instigation of adaptive immune response. Nitric oxide (NO) synthesized by neutrophil nitric oxide synthase (NOS) profoundly modulates their diverse physiological responsibilities furthermore encompassing pathological implications. Neutrophils are the active participants in diverse inflammatory and cardiovascular disorders but neutrophil nitric oxide synthase (NOS) remains enigmatic on various aspects. This review focuses on inducible NOS (iNOS) and makes an attempt to address its potential impact in neutrophil pathophysiology, their differentiation, functionality, and survival. We described the scenario from its expressional modulation, by pro-and anti-inflammatory cytokines governing the extent and duration of neutrophil immune response, to iNOS catalysis, the intracellular compartmentalization, and protein-protein interactions determining its microenvironment, activity and its contribution as a potential signaling protein apart from its role as signal transducer. Further, the relevance of investigating the unexplored facets of iNOS biology in neutrophils and possible prototypes of iNOS regulation is also exemplified in related cellular systems. K E Y W O R D Sinducible nitric oxide synthase, neutrophils, protein interaction, regulation, subcellular localization INTRODUCTIONSince its discovery as endothelium-derived growth factor, NO has been related to a broad spectrum of signaling pathways in diverse pathophysiological, immunomodulatory, 1-3 and pharmacological responses.NO regulates functional attributes of neutrophils modulating their chemotactic, phagocytic, migratory, and apoptotic activities 4 as elaborated in Fig. 1. Neutrophils generate NO at a rate of (10-100) nmoles /5 min/10 6 cells. 5 These comprise 60-70% of the total peripheral leukocytes in humans, contribute significantly to the circulating levels, encompassing a widespread impact on cardiovascular homeostasis.Being capable against invading pathogens, a tumor cell, and alloantigens, NO is an asset to these immunocompetent cells, adding more to their cytotoxic battalion. It has also been demonstrated that NO mediates neutrophil extracellular traps (NET) release at the site of Abbreviations: AL, arginosuccinate lyase; AS, arginosuccinate synthase; Asc, ascorbate; BH 4 , tetrahydrobioptein; CaM, calmodulim; CGD, chronic granulomatous disease; DHA, dehydroascorbate; ETC, electron transport chain; Hsp, heat shock protein; I B, inhibitor kappa B; NLS, nuclear localization signal; PDZ, PSD-95/Disc large/ZO-1; PKC, protein kinase C; RNI, reactive nitrogen intermediates; ROCK, Rho-associated coiled coil containing protein kinase; TGF, tumor growth factor inflammation / infection by augmenting free radical generation. 6 Study by Napimoga et al. 7 depicted that peroxisome proliferator-activated receptor-(PPAR-) reduces neutrophil migration to the acute inflammatory mesenteric lesion as a result of reduction of rolling and adhesion activities of neu...

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Involvement of NO in the failure of neutrophil migration in sepsis induced by Staphylococcus aureus

Cited by 66 publications

References 70 publications

IL-17 Receptor Signaling Is Required to Control Polymicrobial Sepsis

IL-17 Receptor Signaling Is Required to Control Polymicrobial Sepsis

IL-12, but Not IL-18, Is Critical to Neutrophil Activation and Resistance to Polymicrobial Sepsis Induced by Cecal Ligation and Puncture

Inducible nitric oxide synthase: An asset to neutrophils

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