title: Proteinase 3 activity in sputum from subjects with alpha-1-antitrypsin deficiency and COPD.
abstract: Chronic obstructive pulmonary disease (COPD) is associated with tissue damage believed to result from an imbalance between serine proteinases and their inhibitors. Although the role of neutrophil elastase (NE) has been studied, it is likely that other proteinases play a role. The importance of proteinase 3 (PR3) has not been established, as specific substrates have only recently been available. We studied clinically stable subjects with either alpha-1-antitrypsin (A1AT) deficiency or usual COPD with chronic bronchitis. Sol phase sputum was analysed for PR3 activity and concentration, NE activity and concentration, concentrations of airway inhibitors (A1AT, secretory leukoproteinase inhibitor and elafin) and markers of neutrophilic inflammation. 12 patients were also studied during exacerbations. PR3 activity was present in most sputum samples and greater than NE activity (which was largely undetectable) in both subject groups (A1AT deficiency median PR3 128 nM, interquartile range (IQR) 33-558 nM; NE 0 nM, IQR 0-0 nM; p=0.0043; COPD PR3 22 nM, IQR 0-103 nM; NE 0 nM, IQR 0-0 nM; p=0.015). PR3 activity was greater during exacerbations than in the stable state (p=0.037) and correlated with markers of neutrophilic inflammation. The regular identification of PR3 activity in sputum from stable subjects with A1AT deficiency or usual COPD suggests it may play a greater role in the pathophysiology than previously thought.
authors.affiliation: Centre for Translational Inflammation Research, University of Birmingham Research Laboratories, Queen Elizabeth Hospital, Birmingham, UK.
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Sinden
authors.forename: Robert A
authors.initials: RA
authors.lastname: Stockley
mesh_terms: D000368:Aged; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005786:Gene Expression Regulation; D005838:Genotype; D006801:Humans; D007249:Inflammation; D019272:Leukocyte Elastase / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D053146:Myeloblastin / Q000378:metabolism*; D010641:Phenotype; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000378:metabolism*; D012042:Registries; D013183:Sputum / Q000201:enzymology*; D011795:Surveys and Questionnaires; D019896:alpha 1-Antitrypsin Deficiency / Q000175:diagnosis / Q000378:metabolism*
chemical_list: D019272:Leukocyte Elastase; D053146:Myeloblastin