Subepithelial basement membrane immunoreactivity for matrix metalloproteinase 9: Association with asthma severity, neutrophilic inflammation, and wound repair

被引:124
作者
Wenzel, SE
Balzar, S
Cundall, M
Chu, HW
机构
[1] Natl Jewish Med & Res Ctr, Denver, CO 80206 USA
[2] Univ Colorado, Hlth Sci Ctr, Denver, CO USA
关键词
asthma; pathology; matrix metalloproteinase; newtrophils;
D O I
10.1067/mai.2003.1464
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
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 MNIP-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 SKIM MMP-9 staining. Pulmonary function was significantly lower in those asthmatic subjects with SBM staining. Conclusions: These results suggest that localized tissue MMP9 might play an important role in wound repair and cell trafficking. (J Allergy Clin Immunol 2003;111:1345-52.).
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收藏
页码:1345 / 1352
页数:8
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