Danger signals in trauma

Relja, Borna; Mörs, Katharina; Marzi, Ingo

doi:10.1007/s00068-018-0962-3

Cited by 52 publications

(65 citation statements)

References 223 publications

(293 reference statements)

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“…In 2012, in accordance with the newly recognized "sterile SIRS" as a severe complication form in polytraumatized patients, first clues to a critical role of DAMPs in the promotion of those hyperinflammatory responses have been reported [47]. Among those molecules, endogenous DAMPs including high-mobility group box (HMGB) protein 1, heat shock proteins (HSPs), certain members of the S100A family, histones, free nucleic acids, members of the IL-1 cytokine as well as complement family as bona fide intracellular effectors, which upon abundant rapid release alert the environment about cell stress and danger, have already been reported to activate the posttraumatic innate immune responses and drive organ dysfunction(s) after trauma [12,13,46,48].…”

Section: Sirsmentioning

confidence: 99%

“…DAMPs are released from a damaged or diseased cell, and upon their release, they can stimulate a sterile immune or inflammatory response [13,49,69]. Across the tree of life, DAMP-induced immune responses serve as defense strategies aimed at maintaining and restoring homeostasis.…”

Section: Dampsmentioning

confidence: 99%

“…Activation of neutrophils with microbial or inflammatory stimuli results in the release of neutrophil extracellular traps (NETs) [77]. Upon cell death or specific cell activation of hematopoietic and parenchymal cells, extracellular cfDNA as well as DNA-binding proteins (e.g., histones and HMGB1) are released into circulation [13]. Those DNA-binding proteins are also strongly procoagulant and are involved in the pathogenesis of DIC [76,85].…”

Section: Dampsmentioning

confidence: 99%

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Damage-associated molecular patterns in trauma

Relja

Land

2019

Eur J Trauma Emerg Surg

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135

131

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In 1994, the "danger model" argued that adaptive immune responses are driven rather by molecules released upon tissue damage than by the recognition of "strange" molecules. Thus, an alternative to the "self versus non-self recognition model" has been provided. The model, which suggests that the immune system discriminates dangerous from safe molecules, has established the basis for the future designation of damage-associated molecular patterns (DAMPs), a term that was coined by Walter G. Land, Seong, and Matzinger. The pathological importance of DAMPs is barely somewhere else evident as in the posttraumatic or post-surgical inflammation and regeneration. Since DAMPs have been identified to trigger specific immune responses and inflammation, which is not necessarily detrimental but also regenerative, it still remains difficult to describe their "friend or foe" role in the posttraumatic immunogenicity and healing process. DAMPs can be used as biomarkers to indicate and/or to monitor a disease or injury severity, but they also may serve as clinically applicable parameters for optimized indication of the timing for, i.e., secondary surgeries. While experimental studies allow the detection of these biomarkers on different levels including cellular, tissue, and circulatory milieu, this is not always easily transferable to the human situation. Thus, in this review, we focus on the recent literature dealing with the pathophysiological importance of DAMPs after traumatic injury. Since dysregulated inflammation in traumatized patients always implies disturbed resolution of inflammation, so-called model of suppressing/inhibiting inducible DAMPs (SAMPs) will be very briefly introduced. Thus, an update on this topic in the field of trauma will be provided.

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Section: Sirsmentioning

confidence: 99%

Section: Dampsmentioning

confidence: 99%

Section: Dampsmentioning

confidence: 99%

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Damage-associated molecular patterns in trauma

Relja

Land

2019

Eur J Trauma Emerg Surg

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135

131

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“…Briefly, participants in the NTF-Biobank are allowed as defined by the NTF by-laws for a project request on biosamples from the NTF-Biobank and corresponding data from the NTF Database. As indicated in the figure, upon a positive decision by the Review board of the NTF, then, the AUC will manage the provision of the corresponding laboratory and clinical data of effector cells of the immune system further employs a large number of both microbial pathogen-associated molecular patterns (PAMPs) and host alarmins danger-associated molecular patterns (DAMPs) [13][14][15][16][17][18][19][20][21][22][23][24]. Although a large number of endogenous nuclear or cytosolic triggers has been described in the context of the local/systemic posttraumatic and/or noninfectious inflammatory response, which represent key drivers of the late occurring post-injury complications and fatal outcome rates, the knowledge on their variety as well as their precise mechanisms still remains obscure [25][26][27].…”

Section: Current Stagementioning

confidence: 99%

A nationwide fluidics biobank of polytraumatized patients: implemented by the Network “Trauma Research” (NTF) as an expansion to the TraumaRegister DGU® of the German Trauma Society (DGU)

Relja

Huber‐Lang

Griensven

et al. 2019

Eur J Trauma Emerg Surg

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To decrypt the complexity of the posttraumatic immune responses and to potentially identify novel research pathways for exploration, large-scale multi-center projects including not only in vivo and in vitro modeling, but also temporal sample and material collection along with clinical data capture from multiply injured patients is of utmost importance. To meet this gap, a nationwide biobank for fluidic samples from polytraumatized patients was initiated in 2013 by the task force Network "Trauma Research" (Netzwerk Traumaforschung, NTF) of the German Trauma Society (Deutsche Gesellschaft für Unfallchirurgie e.V., DGU). The NTF-Biobank completes the clinical NTF-Biobank Database and complements the TR-DGU with temporal biological samples from multiply injured patients. The concept behind the idea of the NTF-Biobank was to create a robust interface for meaningful innovative basic, translational and clinical research. For the first time, an integrated platform to prospectively evaluate and monitor candidate biomarkers and/or potential therapeutic targets in biological specimens of quality-controlled and documented patients is introduced, allowing reduction in variability of measurements with high impact due to its large sample size. Thus, the project was introduced to systemically evaluate and monitor multiply injured patients for their (patho-)physiological sequalae together with their clinical treatment strategies applied for overall outcome improval.

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“…The multifactorial biological response to tissue injury after severe trauma triggers an uncontrolled inflammatory reaction. Endogenous damage-associated molecular patterns as well as pathogen-associated molecular patterns activate effector cells of the innate immunity [7][8][9][10][11][12][13]. In parallel, a counterbalancing anti-inflammatory response syndrome (CARS) can develop [12,14].…”

Section: Introductionmentioning

confidence: 99%

Regulatory T Cells Modulate CD4 Proliferation after Severe Trauma via IL-10

Sturm

Xanthopoulos

Heftrig

et al. 2020

JCM

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Objective: Severely injured patients frequently develop an immunological imbalance following the traumatic insult, which might result in infectious complications evoked by a persisting immunosuppression. Regulatory T cells (Tregs) maintain the immune homeostasis by suppressing proinflammatory responses, however, their functionality after trauma is unclear. Here, we characterized the role of Tregs in regulating the proliferation of CD4+ lymphocytes in traumatized patients (TP). Methods: Peripheral blood was obtained daily from 29 severely injured TP (Injury Severity Score, ISS ≥16) for ten days following admission to the emergency department (ED). Ten healthy volunteers (HV) served as controls. The frequency and activity of Tregs were assessed by flow cytometry. Proliferation of CD4+ cells was analyzed either in presence or absence of Tregs, or after blocking of either IL-10 or IL-10R1. Results: The frequencies of CD4+CD25high and CD4+CD25+CD127− Tregs were significantly decreased immediately upon admission of TP to the ED and during the following 10 post-injury days. Compared with HV CD4+ T cell proliferation in TP increased significantly upon their admission and on the following days. As expected, CD4+CD25+CD127− Tregs reduced the proliferation of CD4+ cells in HV, nevertheless, CD4+ proliferation in TP was increased by Tregs. Neutralization of IL-10 as well as blocking the IL-10R1 increased further CD4+ T cell proliferation in Tregs-depleted cultures, thereby confirming an IL-10-mediated mechanism of IL-10-regulated CD4+ T cell proliferation. Neutralization of IL-10 in TP decreased CD4+ T cell proliferation in Tregs-depleted cultures, whereas blocking of the IL-10R1 receptor had no significant effects. Conclusions: The frequency of Tregs in the CD4+ T lymphocyte population is reduced after trauma; however, their inductiveness is increased. The mechanisms of deregulated influence of Tregs on CD4+ T cell proliferation are mediated via IL-10 but not via the IL-10R1.

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Danger signals in trauma

Cited by 52 publications

References 223 publications

Damage-associated molecular patterns in trauma

Damage-associated molecular patterns in trauma

A nationwide fluidics biobank of polytraumatized patients: implemented by the Network “Trauma Research” (NTF) as an expansion to the TraumaRegister DGU® of the German Trauma Society (DGU)

Regulatory T Cells Modulate CD4 Proliferation after Severe Trauma via IL-10

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