Imperial College London
Alternate

ProfessorMasaoTakata

Faculty of Medicine, Department of Surgery & Cancer

Magill Chair in Anaesthetics & Head of Division of APMIC
 
 
 
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Contact

 

+44 (0)20 3315 8816m.takata

 
 
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Location

 

G3.46Chelsea and Westminster HospitalChelsea and Westminster Campus

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Summary

 

Publications

Citation

BibTex format

@article{Koh:2021:10.1164/rccm.202009-3545OC,
author = {Koh, MW and Baldi, RF and Soni, S and Handslip, R and Tan, YY and O'Dea, KP and Malesevic, M and McAuley, DF and O'Kane, CM and Patel, BV and Takata, M and Wilson, MR},
doi = {10.1164/rccm.202009-3545OC},
journal = {American Journal of Respiratory and Critical Care Medicine},
pages = {421--430},
title = {Secreted extracellular cyclophilin a is a novel mediator of ventilator induced lung injury.},
url = {http://dx.doi.org/10.1164/rccm.202009-3545OC},
volume = {204},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - RATIONALE: Mechanical ventilation is a mainstay of intensive care but contributes to the mortality of patients through ventilator induced lung injury. Extracellular Cyclophilin A is an emerging inflammatory mediator and metalloproteinase inducer, and the gene responsible for its expression has recently been linked to COVID-19 infection. OBJECTIVES: Here we explore the involvement of extracellular Cyclophilin A in the pathophysiology of ventilator-induced lung injury. METHODS: Mice were ventilated with low or high tidal volume for up to 3 hours, with or without blockade of extracellular Cyclophilin A signalling, and lung injury and inflammation were evaluated. Human primary alveolar epithelial cells were exposed to in vitro stretch to explore the cellular source of extracellular Cyclophilin A, and Cyclophilin A levels were measured in bronchoalveolar lavage fluid from acute respiratory distress syndrome patients, to evaluate clinical relevance. MEASUREMENTS AND MAIN RESULTS: High tidal volume ventilation in mice provoked a rapid increase in soluble Cyclophilin A levels in the alveolar space, but not plasma. In vivo ventilation and in vitro stretch experiments indicated alveolar epithelium as the likely major source. In vivo blockade of extracellular Cyclophilin A signalling substantially attenuated physiological dysfunction, macrophage activation and matrix metalloproteinases. Finally, we found that patients with acute respiratory distress syndrome showed markedly elevated levels of extracellular Cyclophilin A within bronchoalveolar lavage. CONCLUSIONS: Cyclophilin A is upregulated within the lungs of injuriously ventilated mice (and critically ill patients), where it plays a significant role in lung injury. Extracellular Cyclophilin A represents an exciting novel target for pharmacological intervention.
AU  - Koh,MW
AU  - Baldi,RF
AU  - Soni,S
AU  - Handslip,R
AU  - Tan,YY
AU  - O'Dea,KP
AU  - Malesevic,M
AU  - McAuley,DF
AU  - O'Kane,CM
AU  - Patel,BV
AU  - Takata,M
AU  - Wilson,MR
DO  - 10.1164/rccm.202009-3545OC
EP  - 430
PY  - 2021///
SN  - 1073-449X
SP  - 421
TI  - Secreted extracellular cyclophilin a is a novel mediator of ventilator induced lung injury.
T2  - American Journal of Respiratory and Critical Care Medicine
UR  - http://dx.doi.org/10.1164/rccm.202009-3545OC
UR  - https://www.ncbi.nlm.nih.gov/pubmed/33848447
UR  - https://www.atsjournals.org/doi/10.1164/rccm.202009-3545OC
UR  - http://hdl.handle.net/10044/1/88395
VL  - 204
ER  -
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