Zinc Signals Are Essential for Lipopolysaccharide-Induced Signal Transduction in Monocytes

Haase, Hajo; Ober‐Blöbaum, Julia L.; Engelhardt, Gabriela; Hebel, Silke; Heit, Antje; Heine, Holger; Rink, Lothar

doi:10.4049/jimmunol.181.9.6491

Cited by 248 publications

(259 citation statements)

References 59 publications

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“…By contrast, LPS binding to the TLR4 receptor does not trigger Zn import into the macrophage. Instead, it rapidly increases the expression of the ZIP8 importer located on the lysosomal membrane (79,80). However, this action also elevates the free Zn levels in the cytosol, which can trigger the production of inflammatory cytokines, resulting in T-cell proliferation (81,82).…”

Section: Alterations In Host Cu and Zn Status In Response To Bacteriamentioning

confidence: 99%

The Role of Copper and Zinc Toxicity in Innate Immune Defense against Bacterial Pathogens

Djoko¹,

Ong²,

Walker

et al. 2015

Journal of Biological Chemistry

319

263

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Zinc (Zn) and copper (Cu) are essential for optimal innate immune function, and nutritional deficiency in either metal leads to increased susceptibility to bacterial infection. Recently, the decreased survival of bacterial pathogens with impaired Cu and/or Zn detoxification systems in phagocytes and animal models of infection has been reported. Consequently, a model has emerged in which the host utilizes Cu and/or Zn intoxication to reduce the intracellular survival of pathogens. This review describes and assesses the potential role for Cu and Zn intoxication in innate immune function and their direct bactericidal function.Six first row d-block metal ions, manganese (Mn), iron (Fe), cobalt (Co), nickel (Ni), copper (Cu), and zinc (Zn), are essential micronutrients in living organisms. Investigations and discussions of the roles of these trace metals in biology often relate to their acquisition, storage, and incorporation into enzymes. However, conditions where these metal ions are present in excess or are found in the wrong location, resulting in toxicity, have also been described. Thus, there are also systems that sequester, export, and detoxify excess trace metal ions. Today, the concept of trace metal homeostasis, in which various cellular actions maintain the fine balance between nutrition and toxicity, is well developed.Recently, the concept of "nutritional immunity" has emerged in the context of host defense against pathogens. This envisages a role for mechanisms that protect the host from invading pathogens by restricting their ability to acquire key transition metal ions. One example involves lipocalin, which binds siderophores and thereby prevents Fe acquisition by bacterial pathogens (1). Another is calprotectin, which restricts acquisition of Zn or Mn (2). However, what if the host was able to harness the toxic properties of transition metal ions and use them as bactericides? This review explores the evidence for an antimicrobial role for Cu and Zn in the host defense against bacterial pathogens.

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Section: Alterations In Host Cu and Zn Status In Response To Bacteriamentioning

confidence: 99%

The Role of Copper and Zinc Toxicity in Innate Immune Defense against Bacterial Pathogens

Djoko¹,

Ong²,

Walker

et al. 2015

Journal of Biological Chemistry

319

263

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“…In vitro studies using different cell types and zinc concentrations as well as the impact of chelating agents have made it obvious that the influence of zinc cannot be interpreted using a unilateral approach [35]. For instance, a study by Haase et al have revealed that zinc is necessary for the activation of lipopolysaccharide (LPS)-induced NF-κB signalling pathway, whereas chelating zinc with membrane permeable zinc specific chelator TPEN (N,N,N',N'-tetrakis-(2-pyridyl-methyl) ethylenediamine) completely blocked this pathway [36].On the other hand, there is a growing body of literature that supports the role of zinc as a negative regulator of NF-κB signalling pathways.…”

Section: A Nf-κb and Other Signalling Pathwaymentioning

confidence: 99%

“…Whereas the level of intracellular free zinc regulates the rate of dephosphorylation, and hereby the signal intensity of phosphorylation-dependent signalling [46].…”

Section: A Nf-κb and Other Signalling Pathwaymentioning

confidence: 99%

Zinc in Infection and Inflammation

Gammoh¹,

Rink²

2017

Preprint

Self Cite

126

139

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Abstract:Micronutrient homeostasis is a key factor in maintaining a healthy immune system. Zinc is an essential micronutrient that is involved in the regulation of the innate and adaptive immune responses. The main cause of zinc deficiency is malnutrition. Zinc deficiency leads to cell-mediated immune dysfunctions among other manifestations. Consequently, such dysfunctions lead to a worse outcome in the response towards bacterial infection and sepsis. For instance, zinc is an essential component of the pathogen-eliminating signal transduction pathways leading to neutrophil extracellular traps formation, as well as inducing cell-mediated immunity over humoral immunity by regulating specific factors or differentiation. Additionally, zinc deficiency plays a role in inflammation, mainly elevating inflammatory response as well as damage to host tissue. Zinc is involved in the modulation of the proinflammatory response by targeting Nuclear Factor Kappa B, a transcription factor that is the master regulator of proinflammatory responses. It is also involved in controlling oxidative stress and regulating inflammatory cytokines. Zinc plays an intricate function during an immune response and its homeostasis is critical for sustaining proper immune function. This review will summarize the latest findings concerning the role of this micronutrient during the course of infections and inflammatory response and how the immune system modulates zinc depending on different stimuli.

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“…The membrane permeable form, FluoZin-3AM, was used for staining intracellular zinc in alveolar macrophages and epithelial cells. FluoZin-3AM is routinely used to measure zinc in many different cell types (21,23). Cells were stained for 1 hour at room temperature and resulting fluorescence was measured using FACScan flow cytometer (Becton Dickinson, San Jose, CA).…”

Section: Measurement Of Zinc Levelsmentioning

confidence: 99%

Zinc Deficiency Mediates Alcohol-Induced Alveolar Epithelial and Macrophage Dysfunction in Rats

Joshi¹,

Mehta²,

Jabber³

et al. 2009

Am J Respir Cell Mol Biol

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Chronic alcohol abuse impairs both alveolar epithelial and macrophage function, and renders individuals susceptible to acute lung injury, pneumonia, and other serious lung diseases. Zinc deficiency, which is known to impact both epithelial and immune cell functions, is also associated with alcohol abuse. In this study, chronic alcohol ingestion (6 wk) in rats altered expression of key zinc transporters and storage proteins in the small intestine and the lung, and decreased zinc levels in the alveolar compartment. Zinc supplementation of alveolar epithelial monolayers derived from alcohol-fed rats in vitro, or of the diets of alcohol-fed rats in vivo, restored alveolar epithelial barrier function, and these improvements were associated with salutary changes in tight junction protein expression and membrane localization. In parallel, dietary zinc supplementation increased intracellular zinc levels, GM-CSF receptor expression, and bacterial phagocytic capacity in the alveolar macrophages of alcoholfed rats. Together, these studies implicate zinc deficiency as a novel mechanism mediating alcohol-induced alveolar epithelial and macrophage dysfunction. Importantly, these findings argue that dietary supplementation can overcome alcohol-induced zinc deficiency and restore alveolar epithelial and macrophage function, and therefore could be an effective treatment for the susceptible alcoholic lung phenotype.

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Zinc Signals Are Essential for Lipopolysaccharide-Induced Signal Transduction in Monocytes

Cited by 248 publications

References 59 publications

The Role of Copper and Zinc Toxicity in Innate Immune Defense against Bacterial Pathogens

The Role of Copper and Zinc Toxicity in Innate Immune Defense against Bacterial Pathogens

Zinc in Infection and Inflammation

Zinc Deficiency Mediates Alcohol-Induced Alveolar Epithelial and Macrophage Dysfunction in Rats

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