Myeloperoxidase-derived 2-chlorofatty acids contribute to human sepsis mortality via acute respiratory distress syndrome.
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| 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.
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| 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 |
| Journal | JCI insight (JCI Insight) Vol. 2 Issue 23 (12 07 2017) ISSN: 2379-3708 [Electronic] United States |
| PMID | 29212955 (Publication Type: Journal Article, Research Support, N.I.H., Extramural) |
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