Neutrophil extracellular traps and neutrophil-derived mediators as possible biomarkers in bronchial asthma

Clin Exp Med. 2022 May;22(2):285-300. doi: 10.1007/s10238-021-00750-8. Epub 2021 Aug 3.


Neutrophils (PMNs) contain and release a powerful arsenal of mediators, including several granular enzymes, reactive oxygen species (ROS) and neutrophil extracellular traps (NETs). Although airway neutrophilia is associated with severity, poor response to glucocorticoids and exacerbations, the pathophysiological role of neutrophils in asthma remains poorly understood. Twenty-four patients with asthma and 22 healthy controls (HCs) were prospectively recruited. Highly purified peripheral blood neutrophils (> 99%) were evaluated for ROS production and activation status upon stimulation with lipopolysaccharide (LPS), N-formylmethionyl-leucyl-phenylalanine (fMLP) and phorbol 12-myristate 13-acetate (PMA). Plasma levels of myeloperoxidase (MPO), CXCL8, matrix metalloproteinase-9 (MMP-9), granulocyte-monocyte colony-stimulating factor (GM-CSF) and vascular endothelial growth factor (VEGF-A) were measured by ELISA. Plasma concentrations of citrullinated histone H3 (CitH3) and circulating free DNA (dsDNA) were evaluated as NET biomarkers. Activated PMNs from asthmatics displayed reduced ROS production and activation status compared to HCs. Plasma levels of MPO, MMP-9 and CXCL8 were increased in asthmatics compared to HCs. CitH3 and dsDNA plasma levels were increased in asthmatics compared to controls and the CitH3 concentrations were inversely correlated to the % decrease in FEV1/FVC in asthmatics. These findings indicate that neutrophils and their mediators could have an active role in asthma pathophysiology.

Keywords: Asthma; Myeloperoxidase; Neutrophil extracellular traps; ROS.

MeSH terms

  • Asthma* / diagnosis
  • Asthma* / metabolism
  • Biomarkers / metabolism
  • Extracellular Traps* / metabolism
  • Histones / metabolism
  • Humans
  • Matrix Metalloproteinase 9 / metabolism
  • Neutrophils / metabolism
  • Reactive Oxygen Species / metabolism
  • Tetradecanoylphorbol Acetate / metabolism
  • Vascular Endothelial Growth Factor A / metabolism


  • Biomarkers
  • Histones
  • Reactive Oxygen Species
  • Vascular Endothelial Growth Factor A
  • Matrix Metalloproteinase 9
  • Tetradecanoylphorbol Acetate