Molecular and biophysical mechanisms behind the enhancement of lung surfactant function during controlled therapeutic hypothermia

Abstract Therapeutic hypothermia (TH) enhances pulmonary surfactant performance in vivo by molecular mechanisms still unknown. Here, the interfacial structure and the composition of lung surfactant films have been analysed in vitro under TH as well as the molecular basis of its improved performance...

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Autores principales:	C. Autilio, M. Echaide, A. Cruz, C. Mouton, A. Hidalgo, E. Da Silva, D. De Luca, B. Sørli Jorid, J. Perez-Gil
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/bfbe9e8a522b473a947c2c3a4066faac
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spelling	oai:doaj.org-article:bfbe9e8a522b473a947c2c3a4066faac2021-12-02T15:23:06ZMolecular and biophysical mechanisms behind the enhancement of lung surfactant function during controlled therapeutic hypothermia10.1038/s41598-020-79025-32045-2322https://doaj.org/article/bfbe9e8a522b473a947c2c3a4066faac2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79025-3https://doaj.org/toc/2045-2322Abstract Therapeutic hypothermia (TH) enhances pulmonary surfactant performance in vivo by molecular mechanisms still unknown. Here, the interfacial structure and the composition of lung surfactant films have been analysed in vitro under TH as well as the molecular basis of its improved performance both under physiological and inhibitory conditions. The biophysical activity of a purified porcine surfactant was tested under slow and breathing-like dynamics by constrained drop surfactometry (CDS) and in the captive bubble surfactometer (CBS) at both 33 and 37 °C. Additionally, the temperature-dependent surfactant activity was also analysed upon inhibition by plasma and subsequent restoration by further surfactant supplementation. Interfacial performance was correlated with lateral structure and lipid composition of films made of native surfactant. Lipid/protein mixtures designed as models to mimic different surfactant contexts were also studied. The capability of surfactant to drastically reduce surface tension was enhanced at 33 °C. Larger DPPC-enriched domains and lower percentages of less active lipids were detected in surfactant films exposed to TH-like conditions. Surfactant resistance to plasma inhibition was boosted and restoration therapies were more effective at 33 °C. This may explain the improved respiratory outcomes observed in cooled patients with acute respiratory distress syndrome and opens new opportunities in the treatment of acute lung injury.C. AutilioM. EchaideA. CruzC. MoutonA. HidalgoE. Da SilvaD. De LucaB. Sørli JoridJ. Perez-GilNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q C. Autilio M. Echaide A. Cruz C. Mouton A. Hidalgo E. Da Silva D. De Luca B. Sørli Jorid J. Perez-Gil Molecular and biophysical mechanisms behind the enhancement of lung surfactant function during controlled therapeutic hypothermia
description	Abstract Therapeutic hypothermia (TH) enhances pulmonary surfactant performance in vivo by molecular mechanisms still unknown. Here, the interfacial structure and the composition of lung surfactant films have been analysed in vitro under TH as well as the molecular basis of its improved performance both under physiological and inhibitory conditions. The biophysical activity of a purified porcine surfactant was tested under slow and breathing-like dynamics by constrained drop surfactometry (CDS) and in the captive bubble surfactometer (CBS) at both 33 and 37 °C. Additionally, the temperature-dependent surfactant activity was also analysed upon inhibition by plasma and subsequent restoration by further surfactant supplementation. Interfacial performance was correlated with lateral structure and lipid composition of films made of native surfactant. Lipid/protein mixtures designed as models to mimic different surfactant contexts were also studied. The capability of surfactant to drastically reduce surface tension was enhanced at 33 °C. Larger DPPC-enriched domains and lower percentages of less active lipids were detected in surfactant films exposed to TH-like conditions. Surfactant resistance to plasma inhibition was boosted and restoration therapies were more effective at 33 °C. This may explain the improved respiratory outcomes observed in cooled patients with acute respiratory distress syndrome and opens new opportunities in the treatment of acute lung injury.
format	article
author	C. Autilio M. Echaide A. Cruz C. Mouton A. Hidalgo E. Da Silva D. De Luca B. Sørli Jorid J. Perez-Gil
author_facet	C. Autilio M. Echaide A. Cruz C. Mouton A. Hidalgo E. Da Silva D. De Luca B. Sørli Jorid J. Perez-Gil
author_sort	C. Autilio
title	Molecular and biophysical mechanisms behind the enhancement of lung surfactant function during controlled therapeutic hypothermia
title_short	Molecular and biophysical mechanisms behind the enhancement of lung surfactant function during controlled therapeutic hypothermia
title_full	Molecular and biophysical mechanisms behind the enhancement of lung surfactant function during controlled therapeutic hypothermia
title_fullStr	Molecular and biophysical mechanisms behind the enhancement of lung surfactant function during controlled therapeutic hypothermia
title_full_unstemmed	Molecular and biophysical mechanisms behind the enhancement of lung surfactant function during controlled therapeutic hypothermia
title_sort	molecular and biophysical mechanisms behind the enhancement of lung surfactant function during controlled therapeutic hypothermia
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/bfbe9e8a522b473a947c2c3a4066faac
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Molecular and biophysical mechanisms behind the enhancement of lung surfactant function during controlled therapeutic hypothermia

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