Subepithelial basement membrane immunoreactivity for matrix metalloproteinase 9: association with asthma severity, neutrophilic inflammation, and wound repair.
BACKGROUND
Asthma likely involves an active injury and repair process, including components such as neutrophils and matrix metalloproteinase 9 (MMP-9). Although MMP-9 is increased in lavage fluid and sputum in patients with asthma, controversy exists as to the role of tissue MMP-9.


OBJECTIVE
The purpose of this study was to determine whether increases in submucosal cellular MMP-9, matrix MMP-9 (subepithelial basement membrane [SBM]), or both would be associated with severe asthma, neutrophilic inflammation, and wound repair.


METHODS
Immunohistochemical staining and analyses of MMP-9, inflammatory cells, transforming growth factor beta, and collagen I were performed in endobronchial biopsy specimens, bronchoalveolar lavage fluid, or both from 38 patients with severe asthma and compared with results in 10 patients with mild asthma, 8 patients with moderate asthma, and 10 healthy control subjects.


RESULTS
A significantly greater proportion of patients with severe asthma demonstrated MMP-9 staining of the SBM than control subjects (P =.02). Bronchoalveolar lavage MMP-9 levels were also increased in patients with severe asthma (P =.0004). The numbers of submucosal neutrophils and macrophages, but not eosinophils, were significantly higher in asthmatic individuals with MMP-9 staining of the SBM (P =.004 and P =.01, respectively). However, the presence of SBM MMP-9 was associated with a high correlation between lavage and tissue eosinophils (r = 0.58, P =.009). Although the SBM thickness did not differ between groups, higher numbers of transforming growth factor beta-positive cells were seen in subjects with SBM MMP-9 staining. Pulmonary function was significantly lower in those asthmatic subjects with SBM staining.


CONCLUSIONS
These results suggest that localized tissue MMP-9 might play an important role in wound repair and cell trafficking.
Wenzel
Sally E
SE
National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206, USA.
Balzar
Silvana
S
Cundall
Meghan
M
Chu
Hong Wei
HW
D000328:Adult; D001249:Asthma / Q000175:diagnosis / Q000201:enzymology* / Q000276:immunology; D001485:Basement Membrane / Q000201:enzymology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002465:Cell Movement; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology; D008168:Lung / Q000166:cytology / Q000201:enzymology*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000032:analysis* / Q000276:immunology; D009504:Neutrophils / Q000276:immunology*; D020545:Respiratory Mucosa / Q000201:enzymology; D014945:Wound Healing
D020780:Matrix Metalloproteinase 9