Madsen, J;
Panchal, MH;
Mackay, R-MA;
Echaide, M;
Koster, G;
Aquino, G;
Pelizzi, N;
... Postle, AD; + view all
(2018)
Metabolism of a synthetic compared with a natural therapeutic pulmonary surfactant in adult mice.
Journal of Lipid Research
, 59
(10)
pp. 1880-1892.
10.1194/jlr.M085431.
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Abstract
Secreted pulmonary surfactant phosphatidylcholine (PC) has a complex intra-alveolar metabolism that involves uptake and recycling by alveolar type II epithelial cells, catabolism by alveolar macrophages, and loss up the bronchial tree. We compared the in vivo metabolism of animal-derived poractant alfa (Curosurf) and a synthetic surfactant (CHF5633) in adult male C57BL/6 mice. The mice were dosed intranasally with either surfactant (80 mg/kg body weight) containing universally 13C-labeled dipalmitoyl PC (DPPC) as a tracer. The loss of [U13C]DPPC from bronchoalveolar lavage and lung parenchyma, together with the incorporation of 13C-hydrolysis fragments into new PC molecular species, was monitored by electrospray ionization tandem mass spectrometry. The catabolism of CHF5633 was considerably delayed compared with poractant alfa, the hydrolysis products of which were cleared more rapidly. There was no selective resynthesis of DPPC and, strikingly, acyl remodeling resulted in preferential synthesis of polyunsaturated PC species. In conclusion, both surfactants were metabolized by similar pathways, but the slower catabolism of CHF5633 resulted in longer residence time in the airways and enhanced recycling of its hydrolysis products into new PC species.
| Type: | Article |
|---|---|
| Title: | Metabolism of a synthetic compared with a natural therapeutic pulmonary surfactant in adult mice |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1194/jlr.M085431 |
| Publisher version: | https://doi.org/10.1194/jlr.M085431 |
| Language: | English |
| Additional information: | © 2018 Madsen et al. Published by The American Society for Biochemistry and Molecular Biology, Inc. Author’s Choice—Final version open access under the terms of the Creative Commons CC-BY license (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | phosphatidylcholine synthesis, molecular species, stable isotopes, acyl remodeling, mass spectrometr |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health > Neonatology |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10091279 |
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