Blood clotting and traumatic injury with shock mediates complement-dependent neutrophil priming for extracellular ROS, ROS-dependent organ injury and coagulopathy

C. D. Barrett, A. T. Hsu, C. D. Ellson, B. Y.Miyazawa, Y. W. Kong, J. D. Greenwood, S. Dhara, M. D. Neal, J. L. Sperry, Myung (Michelle) S Park, M. J. Cohen, B. S. Zuckerbraun, M. B. Yaffe

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Polymorphonuclear (PMN) leucocytes participate in acute inflammatory pathologies such as acute respiratory distress syndrome (ARDS) following traumatic injury and shock, which also activates the coagulation system systemically. Trauma can prime the PMN nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex for an enhanced respiratory burst, but the relative role of various priming agents in this process remains incompletely understood. We therefore set out to identify mediators of PMN priming during coagulation and trauma-shock and determine whether PMN reactive oxygen species (ROS) generated in this manner could influence organ injury and coagulation. Initial experiments demonstrated that PMN are primed for predominantly extracellular ROS production by products of coagulation, which was abrogated by CD88/C5a receptor(C5aR) inhibition. The importance of this was highlighted further by demonstrating that known PMN priming agents result in fractionally different amounts of extracellular versus intracellular ROS release depending on the agent used. Plasma from trauma patients in haemodynamic shock (n = 10) also primed PMN for extracellular ROS in a C5a-dependent manner, which correlated with both complement alternative pathway activation and thrombin generation. Furthermore, PMN primed by preincubation with products of blood coagulation directly caused loss of endothelial barrier function in vitro that was abrogated by C5aR blockade or NADPH oxidase inhibition. Finally, we show in a murine model of trauma-shock that p47phox knock-out (KO) mice with PMN incapable of generating ROS were protected from inflammatory end-organ injury and activated protein C-mediated coagulopathy. In summary, we demonstrate that trauma-shock and coagulation primes PMN for predominantly extracellular ROS production in a C5a-dependent manner that contributes to endothelial barrier loss and organ injury, and potentially enhances traumatic coagulopathy.

Original languageEnglish (US)
Pages (from-to)103-117
Number of pages15
JournalClinical and Experimental Immunology
Volume194
Issue number1
DOIs
StatePublished - Oct 1 2018

Fingerprint

Blood Coagulation
Shock
Reactive Oxygen Species
Neutrophils
Wounds and Injuries
Anaphylatoxin C5a Receptor
NADP
Oxidoreductases
Traumatic Shock
Alternative Complement Pathway
Respiratory Burst
Adult Respiratory Distress Syndrome
Protein C
Knockout Mice
Thrombin
Hemodynamics
Pathology

Keywords

  • coagulation
  • complement
  • endothelium
  • inflammation
  • NADPH oxidase
  • neutrophil
  • PMN
  • reactive oxygen species
  • trauma

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Blood clotting and traumatic injury with shock mediates complement-dependent neutrophil priming for extracellular ROS, ROS-dependent organ injury and coagulopathy. / Barrett, C. D.; Hsu, A. T.; Ellson, C. D.; Y.Miyazawa, B.; Kong, Y. W.; Greenwood, J. D.; Dhara, S.; Neal, M. D.; Sperry, J. L.; Park, Myung (Michelle) S; Cohen, M. J.; Zuckerbraun, B. S.; Yaffe, M. B.

In: Clinical and Experimental Immunology, Vol. 194, No. 1, 01.10.2018, p. 103-117.

Research output: Contribution to journalArticle

Barrett, CD, Hsu, AT, Ellson, CD, Y.Miyazawa, B, Kong, YW, Greenwood, JD, Dhara, S, Neal, MD, Sperry, JL, Park, MMS, Cohen, MJ, Zuckerbraun, BS & Yaffe, MB 2018, 'Blood clotting and traumatic injury with shock mediates complement-dependent neutrophil priming for extracellular ROS, ROS-dependent organ injury and coagulopathy', Clinical and Experimental Immunology, vol. 194, no. 1, pp. 103-117. https://doi.org/10.1111/cei.13166
Barrett, C. D. ; Hsu, A. T. ; Ellson, C. D. ; Y.Miyazawa, B. ; Kong, Y. W. ; Greenwood, J. D. ; Dhara, S. ; Neal, M. D. ; Sperry, J. L. ; Park, Myung (Michelle) S ; Cohen, M. J. ; Zuckerbraun, B. S. ; Yaffe, M. B. / Blood clotting and traumatic injury with shock mediates complement-dependent neutrophil priming for extracellular ROS, ROS-dependent organ injury and coagulopathy. In: Clinical and Experimental Immunology. 2018 ; Vol. 194, No. 1. pp. 103-117.
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AU - Barrett, C. D.

AU - Hsu, A. T.

AU - Ellson, C. D.

AU - Y.Miyazawa, B.

AU - Kong, Y. W.

AU - Greenwood, J. D.

AU - Dhara, S.

AU - Neal, M. D.

AU - Sperry, J. L.

AU - Park, Myung (Michelle) S

AU - Cohen, M. J.

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AU - Yaffe, M. B.

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