RT Journal Article
SR Electronic
T1 Impaired lung repair during neutropenia can be reverted by matrix metalloproteinase-9
JF Thorax
JO Thorax
FD BMJ Publishing Group Ltd and British Thoracic Society
SP 321
OP 330
DO 10.1136/thoraxjnl-2017-210105
VO 73
IS 4
A1 Jorge Blázquez-Prieto
A1 Inés López-Alonso
A1 Laura Amado-Rodríguez
A1 Covadonga Huidobro
A1 Adrián González-López
A1 Wolfgang M Kuebler
A1 Guillermo M Albaiceta
YR 2018
UL http://thorax.bmj.com/content/73/4/321.abstract
AB Background Neutrophils 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.Methods To 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).Results Lungs 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.Conclusion Release of MMP-9 from neutrophils is required for adequate matrix processing and lung repair.