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Characterization of phospholipid-modified lung surfactant in vitro and in a neonatal ARDS model reveals anti-inflammatory potential and surfactant lipidome signatures.
- Source :
-
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences [Eur J Pharm Sci] 2022 Aug 01; Vol. 175, pp. 106216. Date of Electronic Publication: 2022 May 23. - Publication Year :
- 2022
-
Abstract
- A strong inflammatory immune response drives the lung pathology in neonatal acute respiratory distress syndrome (nARDS). Anti-inflammatory therapy is therefore a promising strategy for improved treatment of nARDS. We demonstrate a new function of the anionic phospholipids POPG, DOPG, and PIP2 as inhibitors of IL-1β release by LPS and ATP-induced inflammasome activation in human monocyte-derived and lung macrophages. Curosurf® surfactant was enriched with POPG, DOPG, PIP2 and the head-group derivative IP3, biophysically characterized and applicability was evaluated in a piglet model of nARDS. The composition of pulmonary surfactant from piglets was determined by shotgun lipidomics screens. After 72 h of nARDS, levels of POPG, DOPG, and PIP2 were enhanced in the respective treatment groups. Otherwise, we did not observe changes of individual lipid species in any of the groups. Surfactant proteins were not affected, with the exception of the IP3 treated group. Our data show that POPG, DOPG, and PIP2 are potent inhibitors of inflammasome activation; their enrichment in a surfactant preparation did not induce any negative effects on lipid profile and reduced biophysical function in vitro was mainly observed for PIP2. These results encourage to rethink the current strategies of improving surfactant preparations by inclusion of anionic lipids as potent anti-inflammatory immune regulators.<br /> (Copyright © 2022. Published by Elsevier B.V.)
- Subjects :
- Animals
Anti-Inflammatory Agents metabolism
Anti-Inflammatory Agents pharmacology
Anti-Inflammatory Agents therapeutic use
Inflammasomes metabolism
Lipidomics
Lung metabolism
Phospholipids pharmacology
Surface-Active Agents
Swine
Pulmonary Surfactants metabolism
Pulmonary Surfactants pharmacology
Respiratory Distress Syndrome
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0720
- Volume :
- 175
- Database :
- MEDLINE
- Journal :
- European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 35618202
- Full Text :
- https://doi.org/10.1016/j.ejps.2022.106216