Ventilator-induced lung injury promotes inflammation within the pleural cavity
File(s)
Supporting information
Accepted version
Author(s)
Type
Journal Article
Abstract
Mechanical ventilation contributes to the morbidity and mortality of patients in intensive care, likely through the exacerbation and dissemination of inflammation. Despite the proximity of the pleural cavity to the lungs and exposure to physical forces, little attention has been paid to its potential as an inflammatory source during ventilation. Here, we investigate the pleural cavity as a novel site of inflammation during ventilator-induced lung injury. Mice were subjected to low or high tidal volume ventilation strategies for up to 3 hours. Ventilation with a high tidal volume significantly increased cytokine and total protein levels in BAL and pleural lavage fluid. In contrast, acid aspiration, explored as an alternative model of injury, only promoted intraalveolar inflammation, with no effect on the pleural space. Resident pleural macrophages demonstrated enhanced activation after injurious ventilation, including upregulated ICAM-1 and IL-1β expression, and the release of extracellular vesicles. In vivo ventilation and in vitro stretch of pleural mesothelial cells promoted ATP secretion, whereas purinergic receptor inhibition substantially attenuated extracellular vesicles and cytokine levels in the pleural space. Finally, labeled protein rapidly translocated from the pleural cavity into the circulation during high tidal volume ventilation, to a significantly greater extent than that of protein translocation from the alveolar space. Overall, we conclude that injurious ventilation induces pleural cavity inflammation mediated through purinergic pathway signaling and likely enhances the dissemination of mediators into the vasculature. This previously unidentified consequence of mechanical ventilation potentially implicates the pleural space as a focus of research and novel avenue for intervention in critical care.
Date Issued
2024-03-21
Date Acceptance
2024-03-21
Citation
American Journal of Respiratory Cell and Molecular Biology, 2024
ISSN
1044-1549
Publisher
American Thoracic Society
Journal / Book Title
American Journal of Respiratory Cell and Molecular Biology
Copyright Statement
© 2024 American Thoracic Society, All Rights Reserved. This is the author’s accepted manuscript made available under a CC-BY licence in accordance with Imperial’s Research Publications Open Access policy (www.imperial.ac.uk/oa-policy)
License URL
Sponsor
Medical Research Council (MRC)
Grant Number
MR/V012207/1
Subjects
1102 Cardiorespiratory Medicine and Haematology
Respiratory System
Publication Status
Published online
Date Publish Online
2024-03-21