Please use this identifier to cite or link to this item: http://hdl.handle.net/1959.13/24637

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Title
Differential proteolytic enzyme activity in eosinophilic and neutrophilic asthma
Author/Creator
Simpson, Jodie Louise;  Scott, Rodney J.;  Boyle, Michael J.;  Gibson, Peter G.
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 I(> 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.
Relation
American Journal of Respiratory and Critical Care Medicine Vol. 172, no. 5, p. 559-565
Date
2005
Publisher
American Lung Association
Keyword(s)
inflammation;  peptide hydrolases;  sputum;  leukocyte protease inhibitor;  matrix metalloproteinases;  tissue;  inhibitor;  inhaled corticosteroids;  airway inflammation;  persistent;  asthma;  epithelial cells;  gene expression;  elastase
Resource Type
journal article
Identifier
http://hdl.handle.net/1959.13/24637
Identifier
ISSN:1535-4970
Language
eng
Reviewed
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Subject
"American Journal of Respiratory and Critical Care Medicine"
 
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