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

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.

Automated summary

In this study, mass spectrometry imaging with high mass resolution and stable isotope labeling was used to analyze spatial distribution of phosphatidylcholine (PC) metabolism in mouse lungs, revealing dysregulated surfactant metabolism and turnover of therapeutic pulmonary surfactants. The dual labeling strategy demonstrated lack of inhibition of endogenous PC synthesis by exogenous surfactant and showed the location of acyl chain remodeling processes leading to formation of polyunsaturated PC lipids. This ability to visualize discrete metabolic events has potential applications in both clinical and experimental studies.