Mitochondrial DNA neutrophil extracellular traps are formed after trauma and subsequent surgery.

McIlroy, DJ; Jarnicki, AG; Au, GG; Lott, N; Smith, DW; Hansbro, PM; Balogh, ZJ

Mitochondrial DNA neutrophil extracellular traps are formed after trauma and subsequent surgery.

McIlroy, DJ Jarnicki, AG Au, GG Lott, N Smith, DW Hansbro, PM Balogh, ZJ

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Publisher:: W B SAUNDERS CO-ELSEVIER INC
Publication Type:: Journal Article
Citation:: Journal of critical care, 2014, 29, (6), pp. 1133.e1-1133.e5
Issue Date:: 2014-12

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Field	Value	Language
dc.contributor.author	McIlroy, DJ
dc.contributor.author	Jarnicki, AG
dc.contributor.author	Au, GG
dc.contributor.author	Lott, N
dc.contributor.author	Smith, DW
dc.contributor.author	Hansbro, PM
dc.contributor.author	Balogh, ZJ
dc.date.accessioned	2021-03-03T05:37:03Z
dc.date.available	2014-07-15
dc.date.available	2021-03-03T05:37:03Z
dc.date.issued	2014-12
dc.identifier.citation	Journal of critical care, 2014, 29, (6), pp. 1133.e1-1133.e5
dc.identifier.issn	0883-9441
dc.identifier.issn	1557-8615
dc.identifier.uri	http://hdl.handle.net/10453/146723
dc.description.abstract	<h4>Introduction</h4>Neutrophil extracellular traps (NETs) have not been demonstrated after trauma and subsequent surgery. Neutrophil extracellular traps are formed from pure mitochondrial DNA (mtDNA) under certain conditions, which is potently proinflammatory. We hypothesized that injury and orthopedic trauma surgery would induce NET production with mtDNA as a structural component.<h4>Methods</h4>Neutrophils were isolated 8 trauma patients requiring orthopedic surgery postinjury and up to 5 days postoperatively. Four healthy volunteers provided positive and negative controls. Total hip replacement patients acted as an uninjured surgical control group. Neutrophil extracellular traps were visualized with DNA (Hoechst 33342TM/Sytox Green/MitoSox/MitoTracker) stains using live cell fluorescence microscopy with downstream quantitative polymerase chain reaction analysis of DNA composition.<h4>Results</h4>Neutrophil extracellular traps were present after injury in all 8 trauma patients. They persisted for 5 days postoperatively. Delayed surgery resulted in NET resolution, but they reformed postoperatively. Total hip replacement patients developed NETs postoperatively, which resolved by day 5. Quantitative polymerase chain reaction analysis of NET-DNA composition revealed that NETs formed after injury and surgery were made of mtDNA with no detectable nuclear DNA component.<h4>Conclusions</h4>Neutrophil extracellular traps formed after major trauma and subsequent surgery contain mtDNA and represent a novel marker of heightened innate immune activation. They could be considered when timing surgery after trauma to prevent systemic NET-induced inflammatory complications.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	W B SAUNDERS CO-ELSEVIER INC
dc.relation.ispartof	Journal of critical care
dc.relation.isbasedon	10.1016/j.jcrc.2014.07.013
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	1103 Clinical Sciences, 1110 Nursing
dc.subject.classification	Emergency & Critical Care Medicine
dc.subject.mesh	Neutrophils
dc.subject.mesh	Humans
dc.subject.mesh	Bacteremia
dc.subject.mesh	Wounds and Injuries
dc.subject.mesh	DNA, Mitochondrial
dc.subject.mesh	Arthroplasty, Replacement, Hip
dc.subject.mesh	Case-Control Studies
dc.subject.mesh	Adult
dc.subject.mesh	Middle Aged
dc.subject.mesh	Male
dc.subject.mesh	Fractures, Bone
dc.subject.mesh	Systemic Inflammatory Response Syndrome
dc.subject.mesh	Extracellular Traps
dc.subject.mesh	Adult
dc.subject.mesh	Arthroplasty, Replacement, Hip
dc.subject.mesh	Bacteremia
dc.subject.mesh	Case-Control Studies
dc.subject.mesh	DNA, Mitochondrial
dc.subject.mesh	Extracellular Traps
dc.subject.mesh	Fractures, Bone
dc.subject.mesh	Humans
dc.subject.mesh	Male
dc.subject.mesh	Middle Aged
dc.subject.mesh	Neutrophils
dc.subject.mesh	Systemic Inflammatory Response Syndrome
dc.subject.mesh	Wounds and Injuries
dc.title	Mitochondrial DNA neutrophil extracellular traps are formed after trauma and subsequent surgery.
dc.type	Journal Article
utslib.citation.volume	29
utslib.location.activity	United States
utslib.for	1103 Clinical Sciences
utslib.for	1110 Nursing
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney
utslib.copyright.status	open_access	*
dc.date.updated	2021-03-03T05:37:02Z
pubs.issue	6
pubs.publication-status	Published
pubs.volume	29
utslib.citation.issue	6

Abstract:

Introduction

Neutrophil extracellular traps (NETs) have not been demonstrated after trauma and subsequent surgery. Neutrophil extracellular traps are formed from pure mitochondrial DNA (mtDNA) under certain conditions, which is potently proinflammatory. We hypothesized that injury and orthopedic trauma surgery would induce NET production with mtDNA as a structural component.

Methods

Neutrophils were isolated 8 trauma patients requiring orthopedic surgery postinjury and up to 5 days postoperatively. Four healthy volunteers provided positive and negative controls. Total hip replacement patients acted as an uninjured surgical control group. Neutrophil extracellular traps were visualized with DNA (Hoechst 33342TM/Sytox Green/MitoSox/MitoTracker) stains using live cell fluorescence microscopy with downstream quantitative polymerase chain reaction analysis of DNA composition.

Results

Neutrophil extracellular traps were present after injury in all 8 trauma patients. They persisted for 5 days postoperatively. Delayed surgery resulted in NET resolution, but they reformed postoperatively. Total hip replacement patients developed NETs postoperatively, which resolved by day 5. Quantitative polymerase chain reaction analysis of NET-DNA composition revealed that NETs formed after injury and surgery were made of mtDNA with no detectable nuclear DNA component.

Conclusions

Neutrophil extracellular traps formed after major trauma and subsequent surgery contain mtDNA and represent a novel marker of heightened innate immune activation. They could be considered when timing surgery after trauma to prevent systemic NET-induced inflammatory complications.

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http://hdl.handle.net/10453/146723