Differential proteolytic enzyme activity in eosinophilic and neutrophilic asthma

Am J Respir Crit Care Med. 2005 Sep 1;172(5):559-65. doi: 10.1164/rccm.200503-369OC. Epub 2005 May 18.


Rationale: Asthma is characterized by both chronic inflammation and remodeling of the airways. Proteases are important mediators of inflammation, cytokine activation, and tissue remodeling.

Objectives: This study investigated matrix metalloproteinase-9 (MMP-9) and neutrophil elastase (NE) enzyme activity in the sputum of subjects with different inflammatory phenotypes of asthma (eosinophilic, neutrophilic, and paucigranulocytic asthma) and in healthy control subjects.

Methods and measurements: Nonsmoking adults with asthma and healthy control subjects underwent hypertonic saline challenge and sputum induction. Selected sputum portions were dispersed with dithiothreitol and assayed for MMP-9 and NE enzyme activity.

Main results: Subjects with eosinophilic asthma had significantly more active MMP-9 (39 ng/ml) compared with those with neutrophilic asthma (10 ng/ml) and control subjects (2.5 ng/ml, p < 0.01). Although there were high levels of total MMP-9 in neutrophilic asthma (5,273 ng/ml), most (> 99%) was inactivated (and bound to tissue inhibitor of metalloproteinase-1). In neutrophilic asthma, more subjects had NE activity (39%) compared with both healthy control subjects (0%), subjects with eosinophilic asthma (6%), or subjects with paucigranulocytic asthma (0%, p < 0.05). There were strong and consistent positive correlations between interleukin-8, neutrophils, and proteolytic enzymes. MMP-9 was inversely correlated with NE (r = -0.93).

Conclusions: Proteolytic enzyme activity in asthma is dependent on the underlying inflammatory phenotype and is differentially regulated with MMP-9 activity a feature of eosinophilic inflammation, and active NE in neutrophilic inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Asthma / immunology*
  • Eosinophils / immunology
  • Humans
  • Interleukin-8 / immunology
  • Leukocyte Elastase / immunology*
  • Male
  • Matrix Metalloproteinase 9 / immunology*
  • Middle Aged
  • Neutrophils / immunology
  • Peptide Hydrolases


  • Interleukin-8
  • Peptide Hydrolases
  • Leukocyte Elastase
  • Matrix Metalloproteinase 9