TY - JOUR AU - Meyer, Nuala J. AU - Reilly, John P. AU - Feng, Rui AU - Christie, Jason D. AU - Hazen, Stanley L. AU - Albert, Carolyn J. AU - Franke, Jacob D. AU - Hartman, Celine L. AU - McHowat, Jane AU - Ford, David A. T1 - Myeloperoxidase-derived 2-chlorofatty acids contribute to human sepsis mortality via acute respiratory distress syndrome PY - 2017/12/07/ AB - 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. JF - JCI Insight JA - JCI Insight SN - 2379-3708 DO - 10.1172/jci.insight.96432 VL - 2 IS - 23 UR - https://doi.org/10.1172/jci.insight.96432 PB - The American Society for Clinical Investigation ER -