Differential proteolytic enzyme activity in eosinophilic and neutrophilic asthma.
BACKGROUND
Asthma is characterized by both chronic inflammation and remodeling of the airways. Proteases are important mediators of inflammation, cytokine activation, and tissue remodeling.


OBJECTIVE
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
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.


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.
Simpson
Jodie L
JL
School of Medical Practice and Population Health, and Medical Genetics, School of Biomedical Science, Hunter Medical Research Institute, The University of Newcastle, Callaghan, Australia. peter.gibson@hnehealth.nsw.gov.au
Scott
Rodney J
RJ
Boyle
Michael J
MJ
Gibson
Peter G
PG
D000293:Adolescent; D000328:Adult; D000368:Aged; D001249:Asthma / Q000276:immunology*; D004804:Eosinophils / Q000276:immunology; D006801:Humans; D016209:Interleukin-8 / Q000276:immunology; D019272:Leukocyte Elastase / Q000276:immunology*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000276:immunology*; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology; D010447:Peptide Hydrolases
D016209:Interleukin-8; D010447:Peptide Hydrolases; D019272:Leukocyte Elastase; D020780:Matrix Metalloproteinase 9