Maisi Päivi, Prikk Kaiu, Sepper Ruth, Pirilä Emma, Salo Tuula, Hietanen Jarkko, Sorsa Timo
Department of Clinical Veterinary Sciences, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland.
APMIS. 2002 Nov;110(11):771-82. doi: 10.1034/j.1600-0463.2002.1101102.x.
The aim of this study was to investigate the involvement of the MT1-MMP/MMP-2 cascade in induced sputum (IS) and bronchoalveolar lavage fluid (BALF) from bronchial asthma (BA) and bronchiectasis (BE) patients and healthy controls. The molecular forms and cellular origins of MT1-MMP and MMP-2 were determined by Western immunoblotting, immunohistochemistry and in situ hybridization. Elevated levels of soluble activated and autocatalyzed MT1-MMP species as well as activated forms of MMP-2 in IS and BALF samples from BA and BE patients were evidenced. The activation degrees of soluble MT1-MMP and MMP-2 were significantly correlated in BA and BE IS and BALF. Only low levels of both these MMPs were observed in healthy control IS and BALF. The co-expression of MMP-2 with MT1-MMP was evidenced by double immunostaining in bronchial epithelial cells, submucosal glandular cells, smooth muscle cells and monocyte/macrophages. The MT1-MMP/MMP-2 cascade is present and active in human inflammatory lung disease fluid and tissue samples. This cascade seemingly reflects the active destructive phases of these chronic lung diseases.
本研究旨在调查MT1-MMP/MMP-2级联反应在支气管哮喘(BA)、支气管扩张(BE)患者及健康对照者的诱导痰(IS)和支气管肺泡灌洗液(BALF)中的参与情况。通过蛋白质免疫印迹法、免疫组织化学和原位杂交确定MT1-MMP和MMP-2的分子形式及细胞来源。结果表明,BA和BE患者的IS和BALF样本中可溶性活化及自催化MT1-MMP种类以及MMP-2活化形式的水平升高。BA和BE的IS及BALF中可溶性MT1-MMP和MMP-2的活化程度显著相关。在健康对照者的IS和BALF中仅观察到这两种MMP的低水平表达。通过双重免疫染色在支气管上皮细胞、黏膜下腺细胞、平滑肌细胞及单核细胞/巨噬细胞中证实了MMP-2与MT1-MMP的共表达。MT1-MMP/MMP-2级联反应存在于人类炎性肺疾病的液体和组织样本中且具有活性。该级联反应似乎反映了这些慢性肺部疾病的活跃破坏阶段。