Succinate Activation of SUCNR1 Predisposes Severely Injured Patients to Neutrophil-Mediated ARDS.

Annals of Surgery
Geoffrey R NunnsChristopher C Silliman

Abstract

Identify the metabolites that are increased in the plasma of severely injured patients that developed ARDS versus severely injured patients that did not, and assay if these increased metabolites prime PMNs and induce pulmonary sequestration in an animal model of ARDS. We hypothesize that metabolic derangement due to advanced shock in critically injured patients leads to the pulmonary sequestration of neutrophils (PMNs), which serves as the first event in the acute respiratory distress syndrome (ARDS). Intracellular metabolites accumulate in the plasma of severely injured patients. Untargeted metabolomics profiling of 67 critically injured patients was completed to establish a metabolic signature associated with ARDS development. Metabolites that signficantly increased were assayed for PMN priming activity in vitro. The metabolites that primed PMNs were tested in a two-event animal model of ARDS to identify a molecular link between circulating metabolites and clinical risk for ARDS. After controlling for confounders, four metabolites significantly increased: creatine, dehydroascorbate, fumarate, and succinate in trauma patients who developed ARDS (p<0.05). Succinate alone primed the PMN oxidase in vitro at physiologically releva...Continue Reading

Citations

Mar 10, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Christine U VohwinkelHolger K Eltzschig

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