Inflammation resolution circuits are uncoupled in acute sepsis and correlate with clinical severity.

Autor:	Jundi B; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital (BWH) and Harvard Medical School, Boston, Massachusetts, USA., Lee DH; Research Laboratory of Electronics, Massachusetts Institute of Technology, Boston, Massachusetts, USA., Jeon H; Research Laboratory of Electronics, Massachusetts Institute of Technology, Boston, Massachusetts, USA., Duvall MG; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital (BWH) and Harvard Medical School, Boston, Massachusetts, USA., Nijmeh J; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital (BWH) and Harvard Medical School, Boston, Massachusetts, USA., Abdulnour RE; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital (BWH) and Harvard Medical School, Boston, Massachusetts, USA., Pinilla-Vera M; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital (BWH) and Harvard Medical School, Boston, Massachusetts, USA., Baron RM; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital (BWH) and Harvard Medical School, Boston, Massachusetts, USA., Han J; Research Laboratory of Electronics, Massachusetts Institute of Technology, Boston, Massachusetts, USA., Voldman J; Research Laboratory of Electronics, Massachusetts Institute of Technology, Boston, Massachusetts, USA., Levy BD; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital (BWH) and Harvard Medical School, Boston, Massachusetts, USA.
Jazyk:	angličtina
Zdroj:	JCI insight [JCI Insight] 2021 Aug 09; Vol. 6 (15). Date of Electronic Publication: 2021 Aug 09.
DOI:	10.1172/jci.insight.148866
Abstrakt:	Sepsis is a critical illness characterized by dysregulated inflammatory responses lacking counter-regulation. Specialized proresolving mediators are agonists for antiinflammation and for promoting resolution, and they are protective in preclinical sepsis models. Here, in human sepsis, we mapped resolution circuits for the specialized proresolving mediators resolvin D1 and resolvin D2 in peripheral blood neutrophils and monocytes, their regulation of leukocyte activation and function ex vivo, and their relationships to measures of clinical severity. Neutrophils and monocytes were isolated from healthy subjects and patients with sepsis by inertial microfluidics and resolvin D1 and resolvin D2 receptor expression determined by flow cytometry. The impact of these resolvins on leukocyte activation was determined by isodielectric separation and leukocyte function by stimulated phagolysosome formation. Leukocyte proresolving receptor expression was significantly higher in sepsis. In nanomolar concentrations, resolvin D1 and resolvin D2 partially reversed sepsis-induced changes in leukocyte activation and function. Principal component analyses of leukocyte resolvin receptor expression and responses differentiated sepsis from health and were associated with measures of sepsis severity. These findings indicate that resolvin D1 and resolvin D2 signaling for antiinflammation and resolution are uncoupled from leukocyte activation in early sepsis and suggest that indicators of diminished resolution signaling correlate with clinical disease severity.
Databáze:	MEDLINE
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