Characterization of phospholipid-modified lung surfactant in vitro and in a neonatal ARDS model reveals anti-inflammatory potential and surfactant lipidome signatures

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.

Highlights

• Hyper-inflammation in the lung is a hallmark of pathophysiologyin neonatal ARDS.
• Anionic phospholipids attenuate inflammation in response to LPS
• Enrichment of surfactant preparations with anionic phospholipids maintains biophysical function.
• MS profiling demonstrates stable lipidome signatures of surfactant in vivo.

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.

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Sarah Kupsch, Lars F. Eggers, Dietmar Spengler, Nicolas Gisch, Torsten Goldmann, Heinz Fehrenbach, Guido Stichtenoth, Martin F. Krause, Dominik Schwudke, Andra B. Schromm,
Characterization of phospholipid-modified lung surfactant in vitro and in a neonatal ARDS model reveals anti-inflammatory potential and surfactant lipidome signatures,
European Journal of Pharmaceutical Sciences, Volume 175, 2022, 106216, ISSN 0928-0987,
https://doi.org/10.1016/j.ejps.2022.106216.

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