Kinetics and Role of Plasma Matrix Metalloproteinase-9 Expression in Acute Lung Injury and the Acute Respiratory Distress Syndrome
Primed neutrophils that are capable of releasing matrix metalloproteinases (MMPs) into the circulation are thought to play a significant role in the pathophysiology of acute respiratory distress syndrome (ARDS). We hypothesized that direct measurement of plasma MMP-9 activity may be a predictor of i...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Ovid Technologies (Wolters Kluwer) - Lippincott Williams & Wilkins
2016
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| Online Access: | http://hdl.handle.net/1721.1/105873 https://orcid.org/0000-0001-9720-8155 https://orcid.org/0000-0002-9547-3251 |
| _version_ | 1826190731581063168 |
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| author | Gautam, Shiva Talmor, Daniel S. Gallagher, Diana C. Barrett, Christopher D Debusk, Michael George Yaffe, Michael B Hsu, Albert Ellson, Chris |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Gautam, Shiva Talmor, Daniel S. Gallagher, Diana C. Barrett, Christopher D Debusk, Michael George Yaffe, Michael B Hsu, Albert Ellson, Chris |
| author_sort | Gautam, Shiva |
| collection | MIT |
| description | Primed neutrophils that are capable of releasing matrix metalloproteinases (MMPs) into the circulation are thought to play a significant role in the pathophysiology of acute respiratory distress syndrome (ARDS). We hypothesized that direct measurement of plasma MMP-9 activity may be a predictor of incipient tissue damage and subsequent lung injury, which was investigated in both an animal model of ARDS and a small cohort of 38 critically ill human patients. In a mouse model of ARDS involving instillation of intratracheal lipopolysaccharide (LPS) to induce lung inflammation, we measured neutrophil-mediated inflammation, along with MMP-9 activity in the airways and lung tissue and MMP-9 expression in the plasma. Neutrophil recruitment, inflammation, and MMP-9 activity in the airways and lung tissue increased throughout the 72 h after LPS instillation, whereas plasma MMP-9 expression was greatest at 12 to 24 h after LPS instillation. The results suggest that the peak in plasma MMP-9 activity may precede the peak of neutrophil inflammation in the airways and lung tissue in the setting of ARDS. Based on this animal study, a retrospective observational cohort study involving 38 patients admitted to a surgical intensive care unit at a tertiary care university hospital with acute respiratory failure requiring intubation and mechanical ventilation was conducted. Plasma samples were collected daily, and MMP-9 activity was compared with lung function as determined by the PaO[subscript 2]/FiO[subscript 2] ratio. In patients who developed ARDS, a notable increase in plasma MMP-9 activity on a particular day correlated with a decrease in the PaO[subscript 2]/FiO[subscript 2] ratio on the following day (r = -0.503, P < 0.006). Taken together, these results suggest that plasma MMP-9 activity changes, as a surrogate for primed neutrophils may have predictive value for the development of ARDS in a selected subset of critically ill patients. |
| first_indexed | 2024-09-23T08:44:31Z |
| format | Article |
| id | mit-1721.1/105873 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T08:44:31Z |
| publishDate | 2016 |
| publisher | Ovid Technologies (Wolters Kluwer) - Lippincott Williams & Wilkins |
| record_format | dspace |
| spelling | mit-1721.1/1058732022-09-30T10:55:27Z Kinetics and Role of Plasma Matrix Metalloproteinase-9 Expression in Acute Lung Injury and the Acute Respiratory Distress Syndrome Gautam, Shiva Talmor, Daniel S. Gallagher, Diana C. Barrett, Christopher D Debusk, Michael George Yaffe, Michael B Hsu, Albert Ellson, Chris Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Barrett, Christopher D Debusk, Michael George Ellson, Christian Yaffe, Michael B Hsu, Albert Primed neutrophils that are capable of releasing matrix metalloproteinases (MMPs) into the circulation are thought to play a significant role in the pathophysiology of acute respiratory distress syndrome (ARDS). We hypothesized that direct measurement of plasma MMP-9 activity may be a predictor of incipient tissue damage and subsequent lung injury, which was investigated in both an animal model of ARDS and a small cohort of 38 critically ill human patients. In a mouse model of ARDS involving instillation of intratracheal lipopolysaccharide (LPS) to induce lung inflammation, we measured neutrophil-mediated inflammation, along with MMP-9 activity in the airways and lung tissue and MMP-9 expression in the plasma. Neutrophil recruitment, inflammation, and MMP-9 activity in the airways and lung tissue increased throughout the 72 h after LPS instillation, whereas plasma MMP-9 expression was greatest at 12 to 24 h after LPS instillation. The results suggest that the peak in plasma MMP-9 activity may precede the peak of neutrophil inflammation in the airways and lung tissue in the setting of ARDS. Based on this animal study, a retrospective observational cohort study involving 38 patients admitted to a surgical intensive care unit at a tertiary care university hospital with acute respiratory failure requiring intubation and mechanical ventilation was conducted. Plasma samples were collected daily, and MMP-9 activity was compared with lung function as determined by the PaO[subscript 2]/FiO[subscript 2] ratio. In patients who developed ARDS, a notable increase in plasma MMP-9 activity on a particular day correlated with a decrease in the PaO[subscript 2]/FiO[subscript 2] ratio on the following day (r = -0.503, P < 0.006). Taken together, these results suggest that plasma MMP-9 activity changes, as a surrogate for primed neutrophils may have predictive value for the development of ARDS in a selected subset of critically ill patients. National Institutes of Health (U.S.) (Grants R01-GM59281, P50-GM68762 and UM1-HL120877) National Institutes of Health (U.S.) (Ruth L. Kirschstein National Research Service Award) 2016-12-19T16:43:36Z 2016-12-19T16:43:36Z 2015-08 Article http://purl.org/eprint/type/JournalArticle 1073-2322 http://hdl.handle.net/1721.1/105873 Hsu, Albert T. et al. “Kinetics and Role of Plasma Matrix Metalloproteinase-9 Expression in Acute Lung Injury and the Acute Respiratory Distress Syndrome:” Shock 44.2 (2015): 128–136. https://orcid.org/0000-0001-9720-8155 https://orcid.org/0000-0002-9547-3251 en_US http://dx.doi.org/10.1097/shk.0000000000000386 Shock Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Ovid Technologies (Wolters Kluwer) - Lippincott Williams & Wilkins PMC |
| spellingShingle | Gautam, Shiva Talmor, Daniel S. Gallagher, Diana C. Barrett, Christopher D Debusk, Michael George Yaffe, Michael B Hsu, Albert Ellson, Chris Kinetics and Role of Plasma Matrix Metalloproteinase-9 Expression in Acute Lung Injury and the Acute Respiratory Distress Syndrome |
| title | Kinetics and Role of Plasma Matrix Metalloproteinase-9 Expression in Acute Lung Injury and the Acute Respiratory Distress Syndrome |
| title_full | Kinetics and Role of Plasma Matrix Metalloproteinase-9 Expression in Acute Lung Injury and the Acute Respiratory Distress Syndrome |
| title_fullStr | Kinetics and Role of Plasma Matrix Metalloproteinase-9 Expression in Acute Lung Injury and the Acute Respiratory Distress Syndrome |
| title_full_unstemmed | Kinetics and Role of Plasma Matrix Metalloproteinase-9 Expression in Acute Lung Injury and the Acute Respiratory Distress Syndrome |
| title_short | Kinetics and Role of Plasma Matrix Metalloproteinase-9 Expression in Acute Lung Injury and the Acute Respiratory Distress Syndrome |
| title_sort | kinetics and role of plasma matrix metalloproteinase 9 expression in acute lung injury and the acute respiratory distress syndrome |
| url | http://hdl.handle.net/1721.1/105873 https://orcid.org/0000-0001-9720-8155 https://orcid.org/0000-0002-9547-3251 |
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