For a study, individuals with cystic fibrosis (CF) had neutrophils attracted to their airways. Airway neutrophils actively exocytose the major granule protease elastase (NE), whose extracellular activity corresponds with lung damage in adolescents and adults with CF. Free extracellular NE activity was only measured in a fraction of patients during childhood, and the exocytic role of airway neutrophils is unknown. To determine the relationship between airway neutrophil NE exocytosis, free extracellular NE activity, and lung damage in children with cystic fibrosis. Researchers used chest computed tomography and the Perth-Rotterdam Annotated Grid Morphometric Analysis for Cystic Fibrosis scoring system to assess lung damage. Flow and imaging cytometry were used to phenotype blood and BAL fluid leukocytes, and spectrophotometric and Förster resonance energy transfer assays were used to assess free extracellular NE activity. Control individuals were children with airway irritation associated with an aerodigestive disease.
Before diagnosing bronchiectasis, children with CF, but not healthy children, had BAL fluid neutrophils with significant exocytosis of main granules. The molecular measure of free extracellular NE activity did not correspond with lung damage (R=0.55; P=0.0008), but this measure of NE exocytosis did. This mismatch could be due to BAL fluid antiproteases inhibiting extracellular NE and binding to leukocytes. All children with CF experience NE exocytosis by airway neutrophils, and its cellular measure is linked to early lung damage. These data suggest that live airway neutrophils play a role in early CF pathogenesis, guiding biomarker development and anti-inflammatory therapy in CF patients.
Reference:www.atsjournals.org/doi/full/10.1164/rccm.201803-0442OC
