Matrix metalloproteinase activation by free neutrophil elastase contributes to bronchiectasis progression in early cystic fibrosis
© ERS 2015. Neutrophil elastase is the most significant predictor of bronchiectasis in early-life cystic fibrosis; however, the causal link between neutrophil elastase and airway damage is not well understood. Matrix metalloproteinases (MMPs) play a crucial role in extracellular matrix modelling and...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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EUROPEAN RESPIRATORY SOC JOURNALS LTD
2015
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| Online Access: | http://hdl.handle.net/20.500.11937/76817 |
| _version_ | 1848763767705305088 |
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| author | Garratt, L.W. Sutanto, E.N. Ling, K.M. Looi, K. Iosifidis, T. Martinovich, K.M. Shaw, N.C. Kicic-Starcevich, E. Knight, D.A. Ranganathan, S. Stick, S.M. Kicic, Anthony |
| author_facet | Garratt, L.W. Sutanto, E.N. Ling, K.M. Looi, K. Iosifidis, T. Martinovich, K.M. Shaw, N.C. Kicic-Starcevich, E. Knight, D.A. Ranganathan, S. Stick, S.M. Kicic, Anthony |
| author_sort | Garratt, L.W. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | © ERS 2015. Neutrophil elastase is the most significant predictor of bronchiectasis in early-life cystic fibrosis; however, the causal link between neutrophil elastase and airway damage is not well understood. Matrix metalloproteinases (MMPs) play a crucial role in extracellular matrix modelling and are activated by neutrophil elastase. The aim of this study was to assess if MMP activation positively correlates with neutrophil elastase activity, disease severity and bronchiectasis in young children with cystic fibrosis. Total MMP-1, MMP-2, MMP-7, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-2 and TIMP-1 levels were measured in bronchoalveolar lavage fluid collected from young children with cystic fibrosis during annual clinical assessment. Active/pro-enzyme ratio of MMP-9 was determined by gelatin zymography. Annual chest computed tomography imaging was scored for bronchiectasis. A higher MMP-9/TIMP-1 ratio was associated with free neutrophil elastase activity. In contrast, MMP-2/TIMP-2 ratio decreased and MMP-1 and MMP-7 were not detected in the majority of samples. Ratio of active/pro-enzyme MMP-9 was also higher in the presence of free neutrophil elastase activity, but not infection. Across the study cohort, both MMP-9/TIMP-1 and active MMP-9 were associated with progression of bronchiectasis. Both MMP-9/TIMP-1 and active MMP-9 increased with free neutrophil elastase and were associated with bronchiectasis, further demonstrating that free neutrophil elastase activity should be considered an important precursor to cystic fibrosis structural disease. |
| first_indexed | 2025-11-14T11:08:42Z |
| format | Journal Article |
| id | curtin-20.500.11937-76817 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-14T11:08:42Z |
| publishDate | 2015 |
| publisher | EUROPEAN RESPIRATORY SOC JOURNALS LTD |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-768172019-11-12T06:13:49Z Matrix metalloproteinase activation by free neutrophil elastase contributes to bronchiectasis progression in early cystic fibrosis Garratt, L.W. Sutanto, E.N. Ling, K.M. Looi, K. Iosifidis, T. Martinovich, K.M. Shaw, N.C. Kicic-Starcevich, E. Knight, D.A. Ranganathan, S. Stick, S.M. Kicic, Anthony Science & Technology Life Sciences & Biomedicine Respiratory System LOWER AIRWAY INFLAMMATION LUNG-DISEASE EPITHELIAL-CELLS YOUNG-CHILDREN CATHEPSIN-G INHIBITORS PSEUDOMONAS EXPRESSION INFANTS SPUTUM © ERS 2015. Neutrophil elastase is the most significant predictor of bronchiectasis in early-life cystic fibrosis; however, the causal link between neutrophil elastase and airway damage is not well understood. Matrix metalloproteinases (MMPs) play a crucial role in extracellular matrix modelling and are activated by neutrophil elastase. The aim of this study was to assess if MMP activation positively correlates with neutrophil elastase activity, disease severity and bronchiectasis in young children with cystic fibrosis. Total MMP-1, MMP-2, MMP-7, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-2 and TIMP-1 levels were measured in bronchoalveolar lavage fluid collected from young children with cystic fibrosis during annual clinical assessment. Active/pro-enzyme ratio of MMP-9 was determined by gelatin zymography. Annual chest computed tomography imaging was scored for bronchiectasis. A higher MMP-9/TIMP-1 ratio was associated with free neutrophil elastase activity. In contrast, MMP-2/TIMP-2 ratio decreased and MMP-1 and MMP-7 were not detected in the majority of samples. Ratio of active/pro-enzyme MMP-9 was also higher in the presence of free neutrophil elastase activity, but not infection. Across the study cohort, both MMP-9/TIMP-1 and active MMP-9 were associated with progression of bronchiectasis. Both MMP-9/TIMP-1 and active MMP-9 increased with free neutrophil elastase and were associated with bronchiectasis, further demonstrating that free neutrophil elastase activity should be considered an important precursor to cystic fibrosis structural disease. 2015 Journal Article http://hdl.handle.net/20.500.11937/76817 10.1183/09031936.00212114 English EUROPEAN RESPIRATORY SOC JOURNALS LTD restricted |
| spellingShingle | Science & Technology Life Sciences & Biomedicine Respiratory System LOWER AIRWAY INFLAMMATION LUNG-DISEASE EPITHELIAL-CELLS YOUNG-CHILDREN CATHEPSIN-G INHIBITORS PSEUDOMONAS EXPRESSION INFANTS SPUTUM Garratt, L.W. Sutanto, E.N. Ling, K.M. Looi, K. Iosifidis, T. Martinovich, K.M. Shaw, N.C. Kicic-Starcevich, E. Knight, D.A. Ranganathan, S. Stick, S.M. Kicic, Anthony Matrix metalloproteinase activation by free neutrophil elastase contributes to bronchiectasis progression in early cystic fibrosis |
| title | Matrix metalloproteinase activation by free neutrophil elastase contributes to bronchiectasis progression in early cystic fibrosis |
| title_full | Matrix metalloproteinase activation by free neutrophil elastase contributes to bronchiectasis progression in early cystic fibrosis |
| title_fullStr | Matrix metalloproteinase activation by free neutrophil elastase contributes to bronchiectasis progression in early cystic fibrosis |
| title_full_unstemmed | Matrix metalloproteinase activation by free neutrophil elastase contributes to bronchiectasis progression in early cystic fibrosis |
| title_short | Matrix metalloproteinase activation by free neutrophil elastase contributes to bronchiectasis progression in early cystic fibrosis |
| title_sort | matrix metalloproteinase activation by free neutrophil elastase contributes to bronchiectasis progression in early cystic fibrosis |
| topic | Science & Technology Life Sciences & Biomedicine Respiratory System LOWER AIRWAY INFLAMMATION LUNG-DISEASE EPITHELIAL-CELLS YOUNG-CHILDREN CATHEPSIN-G INHIBITORS PSEUDOMONAS EXPRESSION INFANTS SPUTUM |
| url | http://hdl.handle.net/20.500.11937/76817 |