Mass spectrometry imaging of phosphatidylcholine metabolism in lungs administered with therapeutic surfactants and isotopic tracers

Shane R. Ellis*, Emily Hall, Madhuriben Panchal, Bryn Flinders, Jens Madsen, Grielof Koster, Ron M. A. Heeren, Howard W. Clark, Anthony D. Postle*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

7 Citations (Web of Science)

Abstract

Mass spectrometry imaging (MSI) visualizes molecular distributions throughout tissues but is blind to dynamic metabolic processes. Here, MSI with high mass resolution together with multiple stable isotope labeling provided spatial analyses of phosphatidylcholine (PC) metabolism in mouse lungs. Dysregulated surfactant metabolism is central to many respiratory diseases. Metabolism and turnover of therapeutic pulmonary surfactants were imaged from distributions of intact and metabolic products of an added tracer, universally C-13-labeled dipalmitoyl PC ((UC)-C-13-DPPC). The parenchymal distributions of newly synthesized PC species were also imaged from incorporations of methyl-D-9-choline. This dual labeling strategy demonstrated both lack of inhibition of endogenous PC synthesis by exogenous surfactant and location of acyl chain remodeling processes acting on the (UC)-C-13-DPPC-labeled surfactant, leading to formation of polyunsaturated PC lipids. This ability to visualize discrete metabolic events will greatly enhance our understanding of lipid metabolism in diverse tissues and has potential application to both clinical and experimental studies.

Original languageEnglish
Article number100023
Number of pages13
JournalJournal of Lipid Research
Volume62
DOIs
Publication statusPublished - 2021

Keywords

  • Pulmonary surfactant
  • lipids
  • isotope labeling
  • matrix-assisted laser desorption/ionization
  • remodeling
  • ARACHIDONIC-ACID METABOLISM
  • PROTEIN-A
  • PHOSPHOLIPID-COMPOSITION
  • ELECTROSPRAY-IONIZATION
  • ALVEOLAR MACROPHAGES
  • TURNOVER
  • CLEARANCE
  • KINETICS
  • TISSUES
  • LIPIDS

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