Salbutamol up-regulates matrix metalloproteinase-9 in the alveolar space in the acute respiratory distress syndrome

2009 ◽  
Vol 37 (7) ◽  
pp. 2242-2249 ◽  
Author(s):  
Cecilia M. O’Kane ◽  
Scott W. McKeown ◽  
Gavin D. Perkins ◽  
Chris R. Bassford ◽  
Fang Gao ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Matrix Metalloproteinase ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Matrix Metalloproteinase 9 ◽  
Alveolar Space ◽  
Metalloproteinase 9

scholarly journals Impaired lung repair during neutropenia can be reverted by matrix metalloproteinase-9

Thorax ◽  
2017 ◽  
Vol 73 (4) ◽  
pp. 321-330 ◽  
Author(s):  
Jorge Blázquez-Prieto ◽  
Inés López-Alonso ◽  
Laura Amado-Rodríguez ◽  
Covadonga Huidobro ◽  
Adrián González-López ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Lung Injury ◽  
Matrix Metalloproteinase ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Ex Vivo ◽  
Matrix Metalloproteinase 9 ◽  
Neutropenic Patients ◽  
Metalloproteinase 9

BackgroundNeutrophils may cause tissue disruption during migration and by releasing cytotoxic molecules. However, the benefits of neutrophil depletion observed in experimental models of lung injury do not correspond with the poor outcome of neutropenic patients.MethodsTo clarify the role of neutrophils during repair, mice with ventilator induced lung injury (VILI) were rendered neutropenic after damage, and followed for 48 hours of spontaneous breathing. Lungs were harvested and inflammatory mediators and matrix metalloproteinases measured. Bronchoalveolar lavage fluid (BALF) from ventilated patients with acute respiratory distress syndrome, with or without neutropenia, was collected, the same mediators measured and their effects in an ex vivo model of alveolar repair studied. Finally, neutropenic mice were treated after VILI with exogenous matrix metalloproteinase-9 (MMP-9).ResultsLungs from neutropenic animals showed delayed repair and displayed higher levels of tumour necrosis factor α, interferon γ and macrophage inflammatory protein 2, and absence of MMP-9. BALF from ventilated neutropenic patients with acute respiratory distress syndrome showed similar results. BALFs from neutropenic patients yielded a delayed closure rate of epithelial wounds ex vivo, which was improved by removal of collagen or addition of exogenous MMP-9. Lastly, treatment of neutropenic mice with exogenous MMP-9 after VILI reduced tissue damage without modifying cytokine concentrations.ConclusionRelease of MMP-9 from neutrophils is required for adequate matrix processing and lung repair.

Early Increased Levels of Matrix Metalloproteinase-9 in Neonates Recovering from Respiratory Distress Syndrome

Neonatology ◽  
2006 ◽  
Vol 89 (1) ◽  
pp. 6-14 ◽  
Author(s):  
Willem A. Dik ◽  
Anton H.L.C. van Kaam ◽  
Tamara Dekker ◽  
Brigitta A.E. Naber ◽  
Daphne J. Janssen ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Matrix Metalloproteinase 9 ◽  
Metalloproteinase 9

scholarly journals Distinct Proteasome Subpopulations in the Alveolar Space of Patients with the Acute Respiratory Distress Syndrome

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
S. U. Sixt ◽  
R. Alami ◽  
J. Hakenbeck ◽  
M. Adamzik ◽  
A. Kloß ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Healthy Subjects ◽  
Distress Syndrome ◽  
Distinct Pattern ◽  
Alveolar Space ◽  
Chromatographic Purification ◽  
Cell Pellet ◽  
First Time

There is increasing evidence that proteasomes have a biological role in the extracellular alveolar space, but inflammation could change their composition. We tested whether immunoproteasome protein-containing subpopulations are present in the alveolar space of patients with lung inflammation evoking the acute respiratory distress syndrome (ARDS). Bronchoalveolar lavage (BAL) supernatants and cell pellet lysate from ARDS patients (n=28) and healthy subjects (n=10) were analyzed for the presence of immunoproteasome proteins (LMP2 and LMP7) and proteasome subtypes by western blot, chromatographic purification, and 2D-dimensional gelelectrophoresis. In all ARDS patients but not in healthy subjects LMP7 and LMP2 were observed in BAL supernatants. Proteasomes purified from pooled ARDS BAL supernatant showed an altered enzyme activity ratio. Chromatography revealed a distinct pattern with 7 proteasome subtype peaks in BAL supernatant of ARDS patients that differed from healthy subjects. Total proteasome concentration in BAL supernatant was increased in ARDS (971 ng/mL±1116 versus59±25;P<0.001), and all fluorogenic substrates were hydrolyzed, albeit to a lesser extent, with inhibition by epoxomicin (P=0.0001). Thus, we identified for the first time immunoproteasome proteins and a distinct proteasomal subtype pattern in the alveolar space of ARDS patients, presumably in response to inflammation.

Latent class analysis-derived subphenotypes are generalisable to observational cohorts of acute respiratory distress syndrome: a prospective study

Thorax ◽  
2021 ◽  
pp. thoraxjnl-2021-217158
Author(s):  
Pratik Sinha ◽  
Kevin L Delucchi ◽  
Yue Chen ◽  
Hanjing Zhuo ◽  
Jason Abbott ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Lung Injury ◽  
Matrix Metalloproteinase ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Latent Class Analysis ◽  
Latent Class ◽  
Distress Syndrome ◽  
Class Analysis ◽  
Early Assessment

RationaleUsing latent class analysis (LCA), two subphenotypes of acute respiratory distress syndrome (ARDS) have consistently been identified in five randomised controlled trials (RCTs), with distinct biological characteristics, divergent outcomes and differential treatment responses to randomised interventions. Their existence in unselected populations of ARDS remains unknown. We sought to identify subphenotypes in observational cohorts of ARDS using LCA.MethodsLCA was independently applied to patients with ARDS from two prospective observational cohorts of patients admitted to the intensive care unit, derived from the Validating Acute Lung Injury markers for Diagnosis (VALID) (n=624) and Early Assessment of Renal and Lung Injury (EARLI) (n=335) studies. Clinical and biological data were used as class-defining variables. To test for concordance with prior ARDS subphenotypes, the performance metrics of parsimonious classifier models (interleukin 8, bicarbonate, protein C and vasopressor-use), previously developed in RCTs, were evaluated in EARLI and VALID with LCA-derived subphenotypes as the gold-standard.ResultsA 2-class model best fit the population in VALID (p=0.0010) and in EARLI (p<0.0001). Class 2 comprised 27% and 37% of the populations in VALID and EARLI, respectively. Consistent with the previously described ‘hyperinflammatory’ subphenotype, Class 2 was characterised by higher proinflammatory biomarkers, acidosis and increased shock and worse clinical outcomes. The similarities between these and prior RCT-derived subphenotypes were further substantiated by the performance of the parsimonious classifier models in both cohorts (area under the curves 0.92–0.94). The hyperinflammatory subphenotype was associated with increased prevalence of chronic liver disease and neutropenia and reduced incidence of chronic obstructive pulmonary disease. Measurement of novel biomarkers showed significantly higher levels of matrix metalloproteinase-8 and markers of endothelial injury in the hyperinflammatory subphenotype, whereas, matrix metalloproteinase-9 was significantly lower.ConclusionPreviously described subphenotypes are generalisable to unselected populations of non-trauma ARDS.

Sign in / Sign up

Export Citation Format

Share Document