TNF α Primes Polymorphonuclear Leukocytes for an Enhanced Respiratory Burst to a Similar Extent As Bacterial Lipopolysaccharide

Schopf, R. E.; Keller, Regine; Rehder, M.; Benes, P; Kallinowski, Fritz; Vaupel, Peter

doi:10.1111/1523-1747.ep12875802

Cited by 11 publications

(7 citation statements)

References 12 publications

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“…It has long been noted that PMN function, especially the respiratory burst, can be dramatically enhanced by priming with variety of agents, including LPS (34). However, the mechanisms involved in the priming processes are still not fully understood.…”

Section: Resultsmentioning

confidence: 99%

“…One example is priming of polymorphonuclear neutrophils (PMN). When preexposed to LPS, PMN are primed, i.e., poised for a dramatically increased level of oxidative radical production elicited by a very weak secondary stimulus, such as the chemotactic factor formyl-methionyl-leucyl-phenylalanine (fMLP) (34). Although the excessive production of reactive oxygen radicals by PMN is necessary for effective killing of invading organisms, it is also associated with tissue damage during inflammation (36).…”

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confidence: 99%

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Lipopolysaccharide-Binding Protein- and CD14-Dependent Activation of Mitogen-Activated Protein Kinase p38 by Lipopolysaccharide in Human Neutrophils Is Associated with Priming of Respiratory Burst

Yan¹,

Al-Hertani²,

Byers³

et al. 2002

Infect Immun

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Neutrophil (PMN) functions can be primed for greatly increased oxidative radical release by exposure to certain agents such as lipopolysaccharide (LPS). Although a variety of signaling pathways involving both tyrosine kinases and mitogen-activated protein (MAP) kinases may be operative, the mechanisms of PMN priming are still not understood. We found that PMN priming was not achieved by treatment of cells with a very low concentration (5 ng/ml) of LPS unless additional "helper" factors were present in plasma (5%). Under these conditions, LPS induced tyrosine phosphorylation of a 38-kDa protein, which was coincident with the MAP kinase p38 action in this situation. LPS-mediated activation of p38 in human PMNs was dependent on the presence of LPS binding protein from plasma and CD14 on the surfaces of the cells. Phosphorylation of p38 was highly correlated with LPS priming of a formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated PMN respiratory burst. Treatment of PMN with the p38-specific inhibitor SB203580 significantly attenuated the respiratory burst in cells primed by LPS and stimulated by fMLP. These results suggest that the LPS signaling pathway leading to p38 activation may be an important mechanism in regulation of PMN priming. The mediator(s) linking CD14 to p38 involves proteins that are functionally sensitive to genistein but insensitive to tyrphostin AG126 and to Src-and Syk-family kinase, protein kinase C, and phosphatidylinositol 3-kinase inhibitors. Elucidating this pathway will provide insight into possible regulation of PMN priming by LPS.

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Lipopolysaccharide-Binding Protein- and CD14-Dependent Activation of Mitogen-Activated Protein Kinase p38 by Lipopolysaccharide in Human Neutrophils Is Associated with Priming of Respiratory Burst

Yan¹,

Al-Hertani²,

Byers³

et al. 2002

Infect Immun

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“…Taking into consideration that one of the most important effects of TNF is the priming of neutrophils to enhance chemotaxis, phagocytosis, and respiratory burst reactions (36)(37)(38), continuous exposure to OMV may prevent TNF-induced influx of neutrophils and neutrophil-mediated clearance of P. gingivalis. However, neutrophil responsiveness to TNF priming in PD patients was equivalent to that in healthy controls (39).…”

Section: Discussionmentioning

confidence: 99%

Porphyromonas gingivalis Outer Membrane Vesicles Induce Selective Tumor Necrosis Factor Tolerance in a Toll-Like Receptor 4- and mTOR-Dependent Manner

et al. 2016

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f Porphyromonas gingivalis is an important member of the anaerobic oral flora. Its presence fosters growth of periodontal biofilm and development of periodontitis. In this study, we demonstrated that lipophilic outer membrane vesicles (OMV) shed from P. gingivalis promote monocyte unresponsiveness to live P. gingivalis but retain reactivity to stimulation with bacterial DNA isolated from P. gingivalis or AIM2 ligand poly(dA·dT). OMV-mediated tolerance of P. gingivalis is characterized by selective abrogation of tumor necrosis factor (TNF). Neutralization of interleukin-10 (IL-10) during OMV challenge partially restores monocyte responsiveness to P. gingivalis; full reactivity to P. gingivalis can be restored by inhibition of mTOR signaling, which we previously identified as the major signaling pathway promoting Toll-like receptor 2 and Toll-like receptor 4 (TLR2/4)-mediated tolerance in monocytes. However, despite previous reports emphasizing a central role of TLR2 in innate immune recognition of P. gingivalis, our current findings highlight a selective role of TLR4 in the promotion of OMV-mediated TNF tolerance: only blockade of TLR4 -and not of TLR2-restores responsiveness to P. gingivalis. Of further note, OMV-mediated tolerance is preserved in the presence of cytochalasin B and chloroquine, indicating that triggering of surface TLR4 is sufficient for this effect. Taking the results together, we propose that P. gingivalis OMV contribute to local immune evasion of P. gingivalis by hampering the host response. P eriodontitis (PD) is probably the most frequent chronic inflammatory disorder associated with an alteration of the local microbiota. Clinically, release of inflammatory mediators induces collagen degradation and bone resorption, which ultimately result in tooth loss. The carbohydrate-deficient subgingival environment fosters the growth of Porphyromonas gingivalis (1). Tissue degradation caused by enzymes released from bacteria and neutrophils provokes an inflammatory response and supplies bacteria with additional nutrients. This specific milieu permits growth of P. gingivalis, whose sophisticated mechanisms for immune evasion enhance growth of the periodontal biofilm, thus leading to bacterial overgrowth and excessive immune stimulation (2, 3).P. gingivalis releases outer membrane lipophilic microvesicles, which contain lipopolysaccharide (LPS) as a major structural component (4-6). These outer membrane vesicles (OMV) overcome the epithelial barrier, thus transporting LPS and other virulence factors into the host tissue (7). Subsequently, OMV elicit a robust mucosal immune response (8), an effect exploited in OMV-based vaccines (8, 9) and mainly attributed to their LPS content (6). However, unlike LPS from Escherichia coli or Salmonella spp., which are Toll-like receptor 4 (TLR4) agonists, P. gingivalis LPS contains a mixture of chemically diverse lipid A species with distinct immune stimulatory properties (10). Albeit P. gingivalis LPS was formerly thought to act as a TLR2 ligand (11, 12), recent studi...

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“…For example, low doses of cytokines (picomolar range) do not cause activation of the respiratory burst. Conversely, they prime these responses in the context of formyl peptides, phorbol esters and opsonized particles [34][35][36].…”

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confidence: 99%

Phagocyte priming by low magnesium status: input to the enhanced inflammatory and oxidative stress responses

Libako

Nowacki²,

Rock³

et al. 2010

Magnesium Research

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Epidemiological and experimental studies underline the role of magnesium in inflammation. Several data indicate an enhanced response of phagocytes (granulocytes, macrophages) derived from magnesium-deficient animals or cultured under low magnesium conditions to the inflammatory mediators' stimulation. On the contrary, it was pointed out that high extracellular Mg 2+ concentration might partially attenuate the activation of phagocyte leukocytes. Thus, it is likely that magnesium-deficient conditions lead to the priming (pre-activation) of phagocytic cells. Magnesium status is an important modulator of the phagocyte response to immune stimuli and consequently could be implicated in a wide range of pathophysiological issues, e.g. those related to the production of radical oxygen species (ROS). It is likely that magnesium directly modulates phagocyte priming by its calcium antagonism and indirectly by its effect on the immunoinflammatory processes, the source of the priming mediators.

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TNF α Primes Polymorphonuclear Leukocytes for an Enhanced Respiratory Burst to a Similar Extent As Bacterial Lipopolysaccharide

Cited by 11 publications

References 12 publications

Lipopolysaccharide-Binding Protein- and CD14-Dependent Activation of Mitogen-Activated Protein Kinase p38 by Lipopolysaccharide in Human Neutrophils Is Associated with Priming of Respiratory Burst

Lipopolysaccharide-Binding Protein- and CD14-Dependent Activation of Mitogen-Activated Protein Kinase p38 by Lipopolysaccharide in Human Neutrophils Is Associated with Priming of Respiratory Burst

Porphyromonas gingivalis Outer Membrane Vesicles Induce Selective Tumor Necrosis Factor Tolerance in a Toll-Like Receptor 4- and mTOR-Dependent Manner

Phagocyte priming by low magnesium status: input to the enhanced inflammatory and oxidative stress responses

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