Acute exacerbations of COPD are associated with significant activation of matrix metalloproteinase 9 irrespectively of airway obstruction, emphysema and infection

Respiratory Research

Daiana Stolz¹  Michael Tamm¹  Michael Roth¹  Spasenija Savic³  Spyros Batzios²  George Karakiulakis²  Eleni Papakonstantinou² 

[1] Clinic of Pulmonary Medicine and Respiratory Cell Research, University Hospital Basel, Petersgraben 4, Basel, 4031, Switzerland;Department of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, 54124, Greece;Institute for Pathology, University Hospital Basel, Schoenbeinstrasse 40, Basel, 4031, Switzerland

关键词: Bronchoalveolar lavage;    Emphysema;    Tissue inhibitor of matrix metalloproteinases;    Matrix metalloproteinases;    Airway obstruction;    Airway remodeling;    COPD exacerbations;   

Others  :  1233539
DOI  :  10.1186/s12931-015-0240-4

 received in 2015-01-08, accepted in 2015-06-19,  发布年份 2015

【 摘 要 】

Background

Acute exacerbations of chronic obstructive pulmonary disease (AE-COPD) are associated with accelerated aggravation of clinical symptoms and deterioration of pulmonary function. The mechanisms by which exacerbations may contribute to airway remodeling and declined lung function are poorly understood. In this study, we investigated if AE-COPD are associated with differential expression of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in bronchoalveolar lavage (BAL).

Methods

COPD patients undergoing diagnostic bronchoscopy, with either stable disease (n = 53) or AE-COPD (n = 44), matched for their demographics and lung function parameters were included in this study. Protein levels of MMP-2,–9,–12 and of TIMP-1 and -2 in BAL were measured by ELISA. Enzymatic activity of MMP-2 and -9 was assessed by gelatin zymography.

Results

We observed that MMP-9, TIMP-1 and TIMP-2 were significantly increased in BAL during AE-COPD. Furthermore, there was a significant negative correlation of MMP-9, TIMP-1 and TIMP-2 with FEV1% predicted and a significant positive correlation of TIMP-1 and TIMP-2 with RV% predicted in AE-COPD. None of MMPs and TIMPs correlated with DLCO% predicted, indicating that they are associated with airway remodeling leading to obstruction rather than emphysema. In AE-COPD the gelatinolytic activity of MMP-2 was increased and furthermore, MMP-9 activation was significantly up-regulated irrespective of lung function, bacterial or viral infections and smoking.

Conclusions

The results of this study indicate that during AE-COPD increased expression of TIMP-1, TIMP-2, and MMP-9 and activation of MMP-9 may be persistent aggravating factors associated with airway remodeling and obstruction, suggesting a pathway connecting frequent exacerbations to lung function decline.

【 授权许可】

   
2015 Papakonstantinou et al.

【 图 表 】

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