The role of Matrix Metalloproteinase-9 (MMP-9) in the pathogenesis of chronic obstructive Pulmonary disease (COPD)

Abstract

This study has investigated the balance between MMP-9 and TIMP-1 in a variety of clinical samples including bronchoalveolar lavage (BAL) fluid, sputum and directly resected parenchymal tissue and dronchial epithelium from COPD patients. Importantly this has given us an insight into the protease: antiprotease balance in different compartments of the lung as well as in different stages of disease progression, both in stable COPD and during exacerbation. Overall we have illustrated that elevated levels of MMP-9 are an important factor in disease; finding elevated MMP-9 in both BAL fluid from COPD patients and the lung tissue of smokers with impaired lung function. Exacerbations or acute worsening of symptoms are important symptomatic events in disease progression, and we have illustrated that MMP-9 levels are augmented during an exacerbation causing a significant imbalance with the inhibitor TIMP-1. During such episodes neutrophil infiltration is likely to be an important source of MMP-9. Additionally, it is possible that neutrophil infiltration related to lymphocyte activity during an exacerbation.

To measure the amount of total TIMP-1 able to bind MMP-9 we have developed a novel inhibitor binding assay. Initial results suggest that amount of active TIMP-1 varies between individuals with COPD, possibly augmenting the proteinase / antiproteinase imbalance further. Additional development of the assay and possible comparison of samples from COPD patients with other lung diseases, as well as samples from normal individuals and remain to be completed.

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