Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
Myeloperoxidase-derived 2-chlorofatty acids contribute to human sepsis mortality via acute respiratory distress syndrome
Nuala J. Meyer, … , Jane McHowat, David A. Ford
Nuala J. Meyer, … , Jane McHowat, David A. Ford
Published December 7, 2017
Citation Information: JCI Insight. 2017;2(23):e96432. https://doi.org/10.1172/jci.insight.96432.
View: Text | PDF
Research Article Infectious disease Inflammation

Myeloperoxidase-derived 2-chlorofatty acids contribute to human sepsis mortality via acute respiratory distress syndrome

  • Text
  • PDF
Abstract

Sepsis-associated acute respiratory distress syndrome (ARDS) is characterized by neutrophilic inflammation and poor survival. Since neutrophil myeloperoxidase (MPO) activity leads to increased plasma 2-chlorofatty acid (2-ClFA) levels, we hypothesized that plasma concentrations of 2-ClFAs would associate with ARDS and mortality in subjects with sepsis. In sequential consenting patients with sepsis, free 2-ClFA levels were significantly associated with ARDS, and with 30-day mortality, for each log increase in free 2-chlorostearic acid. Plasma MPO was not associated with either ARDS or 30-day mortality but was correlated with 2-ClFA levels. Addition of plasma 2-ClFA levels to the APACHE III score improved prediction for ARDS. Plasma 2-ClFA levels correlated with plasma levels of angiopoietin-2, E selectin, and soluble thrombomodulin. Endothelial cells treated with 2-ClFA responded with increased adhesion molecule surface expression, increased angiopoietin-2 release, and dose-dependent endothelial permeability. Our results suggest that 2-ClFAs derived from neutrophil MPO-catalyzed oxidation contribute to pulmonary endothelial injury and have prognostic utility in sepsis-associated ARDS.

Authors

Nuala J. Meyer, John P. Reilly, Rui Feng, Jason D. Christie, Stanley L. Hazen, Carolyn J. Albert, Jacob D. Franke, Celine L. Hartman, Jane McHowat, David A. Ford

×

Figure 1

Septic patients with ARDS display higher day 0 plasma concentrations of free 2-ClFAs.

Options: View larger image (or click on image) Download as PowerPoint
Septic patients with ARDS display higher day 0 plasma concentrations of ...
Compared with subjects who never developed ARDS, those who developed ARDS within the first 6 days of sepsis have higher circulating levels of free 2-ClPA and free 2-ClSA on the day of ICU admission (compared by the Wilcoxon rank-sum test). All values were included in the analyses; however, outliers higher than the y axis are not shown. Box plots show median and 25th and 75th percentile, and whiskers show minima and maxima for each condition. For the ARDS group, 9 and 11 outliers had values above 4 nM 2-ClPA or above 8 nM 2-ClSA, respectively. In the non-ARDS group, there were 2 outliers with values above 8 nM 2-ClSA, but none above 4 nM 2-ClPA.

Copyright © 2023 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts