Overexpression of matrix metalloproteinase-8 and-9 in bronchiectatic airways in vivo

Overexpression of matrix metalloproteinase-8 and-9 in bronchiectatic airways in vivo
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DOI:
10.1183/09031936.02.00282402
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发表时间:
2002-07-01
影响因子:
24.3
通讯作者:
Tsang, KW
Tsang, KW
中科院分区:
医学1区
文献类型:
--
作者:
Zheng, L;Lam, WK;Tsang, KW

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尽管中性粒细胞基质金属蛋白酶(MMPs)在这一过程中的作用鲜为人知,但支气管扩张症的进行性支气管扩张很可能是持续的气道基质破坏的结果。取自25例支气管扩张症患者的支气管内活检,14例对照组的右肺下叶活检。用免疫组织化学方法对肺固有层中的基质金属蛋白酶-8、基质金属蛋白酶-9、中性粒细胞和巨噬细胞进行染色,图像分析系统定量为固有层阳性细胞-mm(-2),发现支气管扩张组固有层的阳性细胞密度明显高于对照组。在支气管扩张的气道中,基质金属蛋白酶-8和基质金属蛋白酶-9阳性细胞的密度相互关联,并与中性粒细胞密度相关,而与巨噬细胞密度无关。在控制航空公司。MMP8与中性粒细胞、MMP9与巨噬细胞密度呈显著正相关,中性粒细胞基质金属蛋白酶在支气管扩张症中的过度表达有助于解释支气管扩张时持续的气道破坏。鉴于基质金属蛋白酶拮抗剂的临床可获得性,本文提出的结果可能对这种无法治疗的疾病的新疗法的开发产生重大影响。
The progressive bronchial dilatation in bronchiectasis is likely to be the result of continued airway matrix destruction, although little is known about the role of neutrophil matrix metalloproteinases (MMPs) in this process.Immunohistochemistry has been used to investigate the expression and cellular localisation of MMP-8 and MMP-9 in bronchiectatic airways in giro. Endobronchial biopsies were taken from 25 bronchiectatic patients, and from the right lower lobe in 14 control subjects. MMP-8, MMP-9, neutrophils and macrophages were stained with monoclonal antibodies and quantified as positive cell-mm(-2) of the lamina propria by using an image analysis system.There were significantly higher densities of MMP-8 and MMP-9 positive cells in the lamina propria of bronchiectatic than control airways. In bronchiectatic airways, the densities of MMP-8 and MMP-9 positive cells correlated with each other and with neutrophil density, but not with macrophage density. In control airways. a significant correlation was found between MMP-8 with neutrophil and MMP-9 with macrophage densities.An overexpression of neutrophil matrix metalloproteinases in bronchiectatic airways could help explain the continuation of airway destruction in bronchiectasis. In view of the clinical availability of matrix metalloproteinase antagonists, the results presented here could have a significant impact on the development of novel therapies of this untreatable disease.