RT Journal Article SR Electronic T1 Presence of progranulin in airway inflammation associated with COPD JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP P628 VO 42 IS Suppl 57 A1 Michael Ungurs A1 Nicola Sinden A1 Rob Stockley YR 2013 UL http://erj.ersjournals.com/content/42/Suppl_57/P628.abstract AB BackgroundProgranulin (PGRN) inhibits neutrophil (PMN) degranulation, however PMN proteinases convert PGRN into pro-inflammatory granulin-peptides (GRNs). PGRN may therefore be central to dysregulated neutrophilic inflammation associated with COPD. The objectives of this study were to study the presence of PGRN and its conversion into GRN-peptides in sputum sol phase samples from patients with COPD.MethodsWestern blots were used to identify PGRN and GRN-peptides in sputum sol phase obtained from patients with a clinical diagnosis of COPD in a clinically stable state. PGRN concentrations in sputum sol phase were measured by ELISA. The proteinase inhibitors A1AT, SLPI and EDTA were added with human recombinant PGRN to sputum sol phase samples to identify the proteinases responsible for PGRN conversion activity.ResultsPGRN and GRN-peptides were present in sputum sol phase and PGRN (nM) correlated negatively with bacterial load (CFU/ml) (r=-0.446, p=0.003, n=43) and markers of neutrophilic inflammation including neutrophil elastase (NE) (nM) (r=-0.562, p=0.008, n=21) and proteinase-3 (PR3) (nM) (r=-0.515, p=0.017, n=21). The PGRN converting activity was blocked by A1AT, but not EDTA and only with SLPI when PR3 activity was absent.ConclusionPGRN and GRN-peptides are present in sputum sol phase, conversion is driven by PR3 and NE. The concentration of PGRN in the airways is associated with the increased inflammation seen with bacterial colonisation as assessed by markers of neutrophilic inflammation.