Traumatic injury is associated with reduced deoxyribonuclease activity and dysregulation of the actin scavenging system

Jon Hazeldine; Robert J Dinsdale; David N Naumann; Animesh Acharjee; Jonathan R B Bishop; Janet M Lord; Paul Harrison

doi:10.1093/burnst/tkab001

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Traumatic injury is associated with reduced deoxyribonuclease activity and dysregulation of the actin scavenging system

更新时间：2022-06-14

- Traumatic injury is associated with reduced deoxyribonuclease activity and dysregulation of the actin scavenging system
- Burns & Trauma Vol. 9, Issue 1, (2021)
- 作者机构：
  
  1. Institute of Inflammation and Ageing, University of Birmingham
  2. National Institute for Health Research Surgical Reconstruction and Microbiology Research Centre, Heritage Building, Queen Elizabeth Hospital Birmingham
  3. Scar Free Foundation Birmingham Centre for Burns Research, University Hospital Birmingham Foundation Trust
  4. Academic Department of Military Surgery and Trauma
  5. Queen Elizabeth Hospital Birmingham
  6. Institute of Cancer and Genomic Sciences
  7. University of Birmingham
- 作者简介：
- 基金信息：
- DOI：10.1093/burnst/tkab001
  CLC：
- Published：2021，
  
  Published Online：1 April 2021，
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Jon Hazeldine, Robert J Dinsdale, David N Naumann, Animesh Acharjee, Jonathan R B Bishop, Janet M Lord, Paul Harrison, Traumatic injury is associated with reduced deoxyribonuclease activity and dysregulation of the actin scavenging system, Burns & Trauma, Volume 9, 2021, tkab001, https://doi.org/10.1093/burnst/tkab001
DOI：

Jon Hazeldine, Robert J Dinsdale, David N Naumann, Animesh Acharjee, Jonathan R B Bishop, Janet M Lord, Paul Harrison, Traumatic injury is associated with reduced deoxyribonuclease activity and dysregulation of the actin scavenging system, Burns & Trauma, Volume 9, 2021, tkab001, https://doi.org/10.1093/burnst/tkab001 DOI：

摘要

Abstract

BackgroundTraumatic injury is associated with increased concentrations of cell-free DNA (cfDNA) in the circulation

which contribute to post-injury complications. The endonuclease deoxyribonuclease 1 (DNase-1) is responsible for removing 90% of circulating cfDNA. Recently

DNase activity was reported to be significantly reduced following major non-traumatic brain injury (TBI)

but the processes responsible were not investigated. Moreover

it is not known how quickly following injury DNase activity is reduced and whether this also occurs after TBI.MethodsAt 3 post-injury time points (≤1

4–12 and 48–72 hours)

blood samples were obtained from 155 adult trauma patients that had sustained an isolated TBI (n = 21)

TBI with accompanying extracranial injury (TBI+) (n = 53) or an extracranial injury only (ECI) (n = 81). In addition to measuring cfDNA levels and the activity and expression of DNase

circulating concentrations of monomeric globular action (G-actin)

an inhibitor of DNase-1

and the actin scavenging proteins gelsolin (GSN) and vitamin D binding protein (VDBP) were determined and values compared to a cohort of healthy controls.ResultsSignificantly elevated concentrations of plasma cfDNA were seen in TBI

TBI+ and ECI patients at all study time points when compared to healthy controls. cfDNA levels were significantly higher at ≤1 hour post-injury in ECI patients who subsequently developed multiple organ dysfunction syndrome when compared to those who did not. Plasma DNase-1 protein was significantly elevated in all patient groups at all sampling time points. In contrast

DNase enzyme activity was significantly reduced

with this impaired function evident in TBI+ patients within minutes of injury. Circulating concentrations of G-actin were elevated in all patient cohorts in the immediate aftermath of injury and this was accompanied by a significant reduction in the levels of GSN and VDBP.ConclusionsThe post-traumatic increase in circulating cfDNA that occurs following extracranial trauma and TBI is accompanied by reduced DNase activity. We propose that

secondary to reduced GSN and VDBP levels

elevated circulating concentrations of G-actin underlie the post-injury reduction in DNase activity. Reducing circulating cfDNA levels via therapeutic restoration of DNase-1 activity may improve clinical outcomes post-injury.

关键词

Keywords

Cell-free DNADeoxyribonucleaseExtracellular actin scavenging systemPre-hospitalTrauma

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