Elastase Exocytosis by Airway Neutrophils Is Associated with Early Lung Damage in Children with Cystic Fibrosis

• DOI: 10.1164/rccm.201803-0442oc
• Publication Date: 2018-10-03T20:43:03Z
• Authors: Camilla Margaroli; Luke W. Garratt; Hamed Horati; A. Susanne Dittrich; Timothy Rosenow; Samuel T. Montgomery; Dario L. Frey; Milton R. Brown; Carsten Schultz; Lokesh Guglani; Anthony Kicic; Limin Peng; Bob J. Scholte; Marcus A. Mall; Hettie M. Janssens; Stephen M. Stick; Rabindra Tirouvan...
• Keywords: Neutrophil elastase

Neutrophils are recruited to the airways of individuals with cystic fibrosis (CF). In adolescents and adults CF, airway neutrophils actively exocytose primary granule protease elastase (NE), whose extracellular activity correlates lung damage. During childhood, free NE is measurable only in a subset patients, exocytic function unknown.To measure exocytosis by relation damage children CF.We measured using chest computed tomography coupled Perth-Rotterdam Annotated Grid Morphometric Analysis for Cystic Fibrosis scoring system. Concomitantly, we phenotyped blood BAL fluid leukocytes flow image cytometry, spectrophotometric Förster resonance energy transfer assays. Children inflammation linked aerodigestive disorder were enrolled as control subjects.Children CF but not disease harbored high granules, before detection bronchiectasis. This correlated (R = 0.55; P 0.0008), whereas molecular did not. discrepancy may be caused inhibition antiproteases its binding leukocytes.NE occurs all cellular early These findings implicate live pathogenesis, which should instruct biomarker development antiinflammatory therapy CF.