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Author Notes:

Jocelyn R. Grunwell, Email: jgrunwe@emory.edu

J.G. and A.F. conceived and developed the study, supervised the acquisition of the biological data, analyzed and interpreted the data. J.G. drafted and edited the manuscript. A.F. assisted with drafting and editing the manuscript. S.S. and A.M. helped with patient sample processing, performed experiments and helped to interpret the data. K.J. and C.O. assisted in identifying, consenting, acquiring patient samples. K.J., C.O., and C.M. assisted in collecting clinical information about the patients. All authors edited and approved the final version of this manuscript.

We acknowledge the Emory + Children’s Flow Cytometry Core for flow cytometry instrumentation. This study was supported in part by the Emory Integrated Genomics Core (EIGC), which is subsidized by the Emory University School of Medicine and is one of the Emory Integrated Core Facilities. Additional support was provided by the Georgia Clinical and Translational Science Alliance of the National Institutes of Health under Award Number UL1TR002378. The content is solely the responsibility of the authors and does not necessarily reflect the official views of the National Institutes of Health. The authors thank the bedside caregivers of the patients involved in this study for their skilled and compassionate care.

The authors declare no competing interests.

Subjects:

Research Funding:

Drs. Grunwell and Fitzpatrick received support for research from the National Institutes of Health. Funding was provided by NIH grants K12HD072245 (Atlanta Pediatric Scholars Program), K23 HL151897-01, and an Emory University Pediatrics Research Alliance Junior Faculty Focused Pilot award to JG.

Keywords:

  • Science & Technology
  • Multidisciplinary Sciences
  • Science & Technology - Other Topics
  • ACUTE LUNG INJURY
  • MORTALITY
  • PATHOGENESIS
  • CONTRIBUTE
  • NETOSIS
  • INNATE
  • RISK
  • DNA

Differential type I interferon response and primary airway neutrophil extracellular trap release in children with acute respiratory distress syndrome

Tools:

Journal Title:

SCIENTIFIC REPORTS

Volume:

Volume 10, Number 1

Publisher:

, Pages 19049-19049

Type of Work:

Article | Final Publisher PDF

Abstract:

Acute respiratory distress syndrome (ARDS) is a heterogeneous condition characterized by the recruitment of large numbers of neutrophils into the lungs. Neutrophils isolated from the blood of adults with ARDS have elevated expression of interferon (IFN) stimulated genes (ISGs) associated with decreased capacity of neutrophils to kill Staphylococcus aureus and worse clinical outcomes. Neutrophil extracellular traps (NETs) are elevated in adults with ARDS. Whether pediatric ARDS (PARDS) is similarly associated with altered neutrophil expression of ISGs and neutrophil extracellular trap release is not known. Tracheal aspirate fluid and cells were collected within 72 h from seventy-seven intubated children. Primary airway neutrophils were analyzed for differential ISG expression by PCR, STAT1 phosphorylation and markers of degranulation and activation by flow cytometry. Airway fluid was analyzed for the release of NETs by myeloperoxidase-DNA complexes using an ELISA. Higher STAT1 phosphorylation, markers of neutrophil degranulation, activation and NET release were found in children with versus without PARDS. Higher NETs were detected in the airways of children with ventilator-free days less than 20 days. Increased airway cell IFN signaling, neutrophil activation, and NET production is associated with PARDS. Higher levels of airway NETs are associated with fewer ventilator-free days.

Copyright information:

© 2020, The Author(s).

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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