Increased HMGB1 expression and release by mononuclear cells following surgical/anesthesia trauma

Manganelli, Valeria; Signore, Michele; Pacini, Ilaria; Misasi, Roberta; Tellan, Guglielmo; Garofalo, Tina; Lococo, Emanuela; Chirletti, Piero; Sorice, Maurizio; Delogu, Giovanna

doi:10.1186/cc9316

Cited by 42 publications

(28 citation statements)

References 36 publications

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“…The release of HMGB1 in inflammation supports the notion of HMGB1 as an endogenous danger signal alerting the immune system to the presence of inflammation and necrosis (33, 34). Germane to the current studies, we demonstrated that there was a significant correlation between CSF mtDNA and HMGB1 concentrations at 24 h after trauma.…”

Section: Discussionsupporting

confidence: 64%

Cerebrospinal Fluid Mitochondrial DNA

Walko¹,

Bola

Hong

et al. 2014

Shock

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Background Danger associated molecular patterns (DAMPs) are nuclear or cytoplasmic proteins that are released from the injured tissues and activate the innate immune system. Mitochondrial DNA (mtDNA) is a novel DAMP that is released into the extracellular milieu subsequent to cell death and injury. We hypothesized that cell death within the central nervous system in children with traumatic brain injury (TBI) would lead to release of mtDNA into the cerebrospinal fluid (CSF) and has the potential to predict the outcome after trauma. Methods CSF was collected from children with severe TBI that required intracranial pressure monitoring with Glasgow Coma Scale (GCS) scores ≤ 8 via an externalized ventricular drain. Control CSF was obtained in children without TBI or meningoencephalitis that demonstrated no leukocytes in the diagnostic lumbar puncture. Results The median age for patients with TBI was 6.3 y and 62% were male. The common mechanisms of injury included motor vehicle collision (35.8%) followed by falls (21.5%) and inflicted TBI (19%); 6 children (14.2%) died during their ICU course. The mean CSF mtDNA concentration was 1.10E +05 ± 2.07E+05 and 1.63E+03 ± 1.80E+03 copies/µL in the pediatric TBI and control population respectively. Furthermore, the mean CSF mtDNA concentration in pediatric patients who later died or had severe disability was significantly higher than that of the survivors (1.63E+ 05 ± 2.77E+05 vs. 5.05E+04 ± 6.21E+04 copies/µL) (p<0.0001). We found a significant correlation between CSF mtDNA and HMGB1, another prototypical DAMP, concentrations (ρ = 0.574, p<0.05), supporting the notion that both DAMPs are increased in the CSF following TBI. Conclusions Our data suggest that CSF mtDNA is novel DAMP in TBI, and appears to be a useful biomarker that correlates with neurological outcome after TBI. Further inquiry into the components of mtDNA that modulate the innate immune response will be helpful in understanding the mechanism of local and systemic inflammation after TBI.

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Section: Discussionsupporting

confidence: 64%

Cerebrospinal Fluid Mitochondrial DNA

Walko¹,

Bola

Hong

et al. 2014

Shock

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“…31 HMGB1 is not only passively released in response to heat-induced cell death, but also actively induces the secretion of inflammatory mediators (ie, cytokines) by various cellular residents of the transitional zone, such as monocytes, 32 neutrophils, 33 and endothelial cells. This hypothesis is supported by a recent study that measured significantly higher plasma HMGB1 levels in burned patients as compared with control (nonburned) patients.…”

Section: Discussionmentioning

confidence: 99%

Immediate Burn Excision Fails to Reduce Injury Progression

Macri

Singer

Taira

et al. 2013

Journal of Burn Care & Research

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The contact thermal injury model in the pig was used to determine whether immediate burn excision could alter the extent of injury progression. It was hypothesized that immediate excision of burns would prevent or reduce tissue necrosis in the uninjured interspaces. Four comb burns were created on the back of each animal, using a brass comb preheated in hot water (100 °C) for 5 minutes. This brass comb produced four distinctive burns sites separated by three "interspaces" of unburned skin, which were to undergo progressive injury. Immediately after burn creation, half of the full-thickness burns were excised leaving the unburned interspaces intact. Two full-thickness excisional wounds per pig with the dimensions identical to the comb burns were included as controls. Burn injury progression was microscopically assessed and reported as the percentage of unburned interspaces that progressed to full-thickness necrosis 7 days after injury. Scar formation was grossly evaluated on day 28 after injury and reported as the total surface area (in square centimeters) of the scar. A total of 24 combs with 72 interspaces were evenly distributed among the three groups. The unburned interspaces of both comb burns and excised comb burns had undergone progressive injury and were 100% dead (24/24; i.e., necrotic and/or apoptotic) 7 days postinjury (95% confidence interval, 86-100%) for both. However, interspaces of the control excisional wounds maintained complete viability, that is, no necrosis or apoptosis (0/24 [0%]; 95% confidence interval, 0-14%; P < .001). There was no significant difference in both surface area and depth of scar resulting from excised and nonexcised comb burns. Immediate burn excision neither prevented nor limited burn injury progression.

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“…In addition, HMGB1 can be passively released from damaged cells [30] following sterile tissue injury resulting from ischemia/reperfusion [31–33], non-penetrating trauma [34–36], or exposure of toxic chemicals to the liver [37–41]. As a DAMP, extracellular HMGB1 passively released by necrotic cells allows innate immune cells to respond to sterile injury (Figure 1) [42;43].…”

Section: Hmgb1 As a Late Mediator Of Experimental Sepsismentioning

confidence: 99%

Targeting HMGB1 in the treatment of sepsis

Wang

Ward

Sama

2014

Expert Opinion on Therapeutic Targets

124

102

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Introduction Sepsis refers to the host’s deleterious and non-resolving systemic inflammatory response to microbial infections, and represents the leading cause of death in the intensive care unit. The pathogenesis of sepsis is complex, but partly mediated by a newly identified alarmin molecule, the high mobility group box 1 (HMGB1). Areas covered Here we review the evidence that support extracellular HMGB1 as a late mediator of experimental sepsis with a wider therapeutic window, and discuss the therapeutic potential of HMGB1-neutralizing antibodies and small molecule inhibitors (herbal components) in experimental sepsis. Expert opinion It will be important to evaluate the efficacy of HMGB1-targeting strategies for the clinical management of human sepsis in the future.

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Increased HMGB1 expression and release by mononuclear cells following surgical/anesthesia trauma

Cited by 42 publications

References 36 publications

Cerebrospinal Fluid Mitochondrial DNA

Cerebrospinal Fluid Mitochondrial DNA

Immediate Burn Excision Fails to Reduce Injury Progression

Targeting HMGB1 in the treatment of sepsis

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