Proteinase 3, a potent secretagogue in airways, is present in cystic fibrosis sputum

Am J Respir Cell Mol Biol. 1999 Apr;20(4):729-36. doi: 10.1165/ajrcmb.20.4.3371.


We evaluated the roles of proteinase 3 (PR3) and human neutrophil elastase (HNE), two neutrophil serine proteinases in the mechanisms leading to airway inflammation and hypersecretion in cystic fibrosis (CF). Using specific enzyme-linked immunosorbent assay (ELISA), we found higher levels of PR3 than HNE in sputum from CF patients. Using two inhibitors, ICI (Imperial Chemical Industries) 200,355 (which inhibits both HNE and PR3) and secretory leukoproteinase inhibitor (SLPI) (which inhibits only HNE), we showed that PR3 was enzymatically active in sputum, and its activity, as assessed by SLPI-resistant serine proteinase activity, correlated highly with its antigenic concentration measured by ELISA. Interestingly, sputum pellet-associated serine proteinase activity was mostly due to HNE. PR3 purified from neutrophil azurophil granules triggered airway gland secretion, as measured by the release of radiolabeled molecules from cultured bovine tracheal serous cells pulse-labeled with Na235SO4. This secretory activity was inhibited by ICI 200,355. PR3 concentration in CF sputum was highly correlated with taurine concentration, a reliable marker of airway inflammation and respiratory scores (e.g., FEV1%), whereas no significant correlation was observed with HNE. We verified that Pseudomonas aeruginosa proteinases did not interfere with the assessment of PR3 and HNE. Indeed, the PR3/HNE ratio was greatest in patients chronically infected by P. aeruginosa. We suggest that PR3 may play a role in the hypersecretory process that is characteristic of CF.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Cattle
  • Cells, Cultured
  • Child
  • Cystic Fibrosis / complications
  • Cystic Fibrosis / enzymology*
  • Cytoplasmic Granules / enzymology
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Leukocyte Elastase / analysis
  • Leukocyte Elastase / metabolism*
  • Myeloblastin
  • Neutrophils / enzymology
  • Oligopeptides / pharmacology
  • Proteinase Inhibitory Proteins, Secretory
  • Proteins / pharmacology
  • Pseudomonas Infections / complications*
  • Pseudomonas Infections / enzymology
  • Salivary Proteins and Peptides / pharmacology
  • Salivary Proteins and Peptides / physiology
  • Secretory Leukocyte Peptidase Inhibitor
  • Serine Endopeptidases / analysis
  • Serine Endopeptidases / metabolism*
  • Serine Proteinase Inhibitors / pharmacology
  • Sputum / enzymology*
  • Trachea / cytology
  • Trachea / physiology


  • Oligopeptides
  • Proteinase Inhibitory Proteins, Secretory
  • Proteins
  • SLPI protein, human
  • Salivary Proteins and Peptides
  • Secretory Leukocyte Peptidase Inhibitor
  • Serine Proteinase Inhibitors
  • ICI 200355
  • Serine Endopeptidases
  • Leukocyte Elastase
  • Myeloblastin