- Title
- Differential proteolytic enzyme activity in eosinophilic and neutrophilic asthma
- Creator
- Simpson, Jodie L.; Scott, Rodney; Boyle, Michael J.; Gibson, Peter G.
- Relation
- American Journal of Respiratory and Critical Care Medicine Vol. 172, Issue 5, p. 559-565
- Publisher Link
- http://dx.doi.org/10.1164/rccm.200503-369OC
- Publisher
- American Lung Association
- Resource Type
- journal article
- Date
- 2005
- Description
- 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 sujects 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.
- Subject
- inflammation; peptide hydrolases; sputum
- Identifier
- http://hdl.handle.net/1959.13/27395
- Identifier
- uon:1628
- Identifier
- ISSN:1535-4970
- Language
- eng
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