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dc.contributor.authorGautam, Shiva
dc.contributor.authorTalmor, Daniel S.
dc.contributor.authorGallagher, Diana C.
dc.contributor.authorBarrett, Christopher D
dc.contributor.authorDebusk, Michael George
dc.contributor.authorEllson, Christian
dc.contributor.authorYaffe, Michael B
dc.contributor.authorHsu, Albert
dc.date.accessioned2016-12-19T16:43:36Z
dc.date.available2016-12-19T16:43:36Z
dc.date.issued2015-08
dc.identifier.issn1073-2322
dc.identifier.urihttp://hdl.handle.net/1721.1/105873
dc.description.abstractPrimed 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.en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grants R01-GM59281, P50-GM68762 and UM1-HL120877)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Ruth L. Kirschstein National Research Service Award)en_US
dc.language.isoen_US
dc.publisherOvid Technologies (Wolters Kluwer) - Lippincott Williams & Wilkinsen_US
dc.relation.isversionofhttp://dx.doi.org/10.1097/shk.0000000000000386en_US
dc.rightsCreative Commons Attribution-Noncommercial-Share Alikeen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/en_US
dc.sourcePMCen_US
dc.titleKinetics and Role of Plasma Matrix Metalloproteinase-9 Expression in Acute Lung Injury and the Acute Respiratory Distress Syndromeen_US
dc.typeArticleen_US
dc.identifier.citationHsu, 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.en_US
dc.contributor.departmentDavid H. Koch Institute for Integrative Cancer Research at MITen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineeringen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.mitauthorBarrett, Christopher D
dc.contributor.mitauthorDebusk, Michael George
dc.contributor.mitauthorEllson, Christian
dc.contributor.mitauthorYaffe, Michael B
dc.contributor.mitauthorHsu, Albert
dc.relation.journalShocken_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsHsu, Albert T.; Barrett, Christopher D.; DeBusk, George M.; Ellson, Christian D.; Gautam, Shiva; Talmor, Daniel S.; Gallagher, Diana C.; Yaffe, Michael B.en_US
dspace.embargo.termsNen_US
dc.identifier.orcidhttps://orcid.org/0000-0001-9720-8155
dc.identifier.orcidhttps://orcid.org/0000-0002-9547-3251
mit.licenseOPEN_ACCESS_POLICYen_US


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