Subepithelial basement membrane immunoreactivity for matrix metalloproteinase 9: Association with asthma severity, neutrophilic inflammation, and wound repair
Subepithelial basement membrane immunoreactivity for matrix metalloproteinase 9: Association with asthma severity, neutrophilic inflammation, and wound repair
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DOI：
10.1067/mai.2003.1464
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发表时间：
2003-06-01
影响因子：
14.2
通讯作者：
Chu, HW
中科院分区：
文献类型：
--
作者：
Wenzel, SE;Balzar, S;Chu, HW
背景资料：哮喘可能涉及主动损伤和修复过程，包括中性粒细胞和基质金属蛋白酶9（MMP-9）等成分。虽然MMP-9在哮喘患者的灌洗液和痰液中增加，但关于组织MMP-9的作用存在争议。目的：本研究的目的是确定是否增加粘膜下细胞MMP-9，基质MMP-9（上皮下基底膜[SBM]），或两者都与严重哮喘，嗜酸性炎症和伤口修复有关。对支气管内活检标本、支气管肺泡灌洗液、支气管肺泡灌洗液和支气管肺泡灌洗液中的MMP-9、炎性细胞、转化生长因子β和I型胶原进行免疫组织化学染色和分析，结果：与对照组相比，重度哮喘患者SBM中MMP-9染色的比例显著增加（P = 0.02），轻度哮喘患者SBM中MMP-9染色的比例显著增加（P = 0.05），中度哮喘患者SBM中MMP-9染色的比例显著增加（P = 0.02）。重度哮喘患者支气管肺泡灌洗液MMP-9水平也升高（P = 0.0004）。MMP-9染色的哮喘患者黏膜下中性粒细胞和巨噬细胞的数量显著高于正常对照组（P = 0.004和P = 0.01），但嗜酸性粒细胞的数量没有显著增加。然而，SBM MNIP-9的存在与灌洗和组织嗜酸性粒细胞之间的高度相关性相关（r = 0.58，P = 0.009）。尽管SBM厚度在组间没有差异，但在SKIM MMP-9染色的受试者中观察到更高数量的转化生长因子β阳性细胞。SBM染色显示哮喘患者肺功能明显降低。结论：这些结果表明，局部组织MMP 9可能在创伤修复和细胞运输中发挥重要作用。（J Allergy Clin Immunol 2003;111：1345-52.）。
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.).