Poor clinical outcomes in alcoholic hepatitis (AH) were correlated with inflammation and neutrophil levels. For a study, researchers sought to determine how neutrophils affected AH liver injury.

In order to study neutrophil extracellular traps (NETs), they extracted blood neutrophils from AH patients and carried out RNA sequencing to investigate special properties.

In AH, they discovered a substantial rise in NET output. Additionally, they discovered a distinct low-density neutrophil (LDNs) population that was absent in healthy controls in AH patients and mice given alcohol. Peripheral LDNs and high-density neutrophils (HDNs) from AH patients were subjected to transcriptome analysis, which demonstrated that HDNs were activated and LDNs had a functionally exhausted phenotype. In fact, they discovered that AH HDNs had greater levels of reactive oxygen species (ROS) at rest and create more ROS in response to LPS stimulation than control HDNs, although AH LDNs did not. They demonstrate that, following alcohol-induced NET release in vitro, HDNs were converted into LDNs, and the LDN subgroup had lower functioning, including diminished phagocytosis. Additionally, LDNs had decreased homing ability and clearance by macrophage efferocytosis, which allowed for the possibility of residual defective neutrophils in the circulation and liver. Treatment with granulocyte-colony stimulating factor (G-CSF) also reduced the liver damage caused by alcohol. 

Neutrophils stimulated the synthesis of NET, which increased the amount of faulty LDNs in AH and causes liver damage. Alcohol altered the phenotype of neutrophils; HDNs were activated while LDNs were deficient. The research offered a mechanistic understanding of therapeutic AH treatments.

Reference: journal-of-hepatology.eu/article/S0168-8278(22)03060-4/fulltext

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