Altered phosphotidylcholine synthetic pathways in patients with acute respiratory distress syndrome

Dushianthan, A., Cusack, R., Goss, V., Postle, A. D. and Grocott, M. P. W. (2013) Altered phosphotidylcholine synthetic pathways in patients with acute respiratory distress syndrome. British Journal of Anaesthesia, 110 (5), 879-880. (doi:10.1093/bja/aes490).

Abstract

Phosphatidylcholines are integral part of pulmonary surfactant and cellular membranes and are synthesised de novo by two clinically distinct pathways. The molecular specificity of PC output varies between these pathways, where mono and di-unsaturated PC species are predominantly generated by the cytidine diphosphate choline (CDP-choline) pathway and polyunsaturated fatty acids (PUFA) by phosphatidylethanolamine-N-methyltransferase (PEMT) pathway. PUFA are capable of generating eicosanoids and have been long recognised as mediators of inflammation in various acute and chronic inflammatory conditions. ARDS is characterised by acute overwhelming inflammatory process and alterations in eicosanoid profile is a recognised feature. Consequently, this study was aimed to assess the molecular specificity of PEMT pathway in patients with severe ARDS. We recruited 10 patients with severe ARDS (Pa02/Fi02 <100mmHg) and 10 healthy controls. Both groups were infused with a natural isotope of choline (methyl-D9-choline chloride). Blood samples were taken at serial time points until day 96 hours of recruitment. Samples were centrifuged and the supernatant was lipid extracted. This was analysed in electro-spray ionisation mass spectrometry where the phosphocholine head group was identified by m/z+184 and subsequent m/z +187 for one and m/z+190 for two deuteriated methyl groups incorporations. From this, we estimated quantitative flux through PEMT pathway for all patients. At maximal synthesis, there was a significant reduction in total PC synthesis in patients via PEMT pathway (44% absolute reduction). This was coupled with reductions in the rate of total PC synthesis and absolute concentrations of PUFA based PC species in plasma. The molecular specificity of PC synthesis was similar for both groups, where PUFA species (E.g. 20:4 and 22:6) were highly selective through this pathway. In conclusion, there are significant alterations in PC synthetic pathways in patients with ARDS. Therapeutic modulation of PUFA may moderate inflammatory process in ARDS. Acknowledgement This study was supported by Southampton NIHR Respiratory Biomedical Research Unit and The National Institute of Academic Anaesthesia (NIAA), UK.

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Contributors

Author: A. Dushianthan

Author: R. Cusack

Author: A. D. Postle

Author: M. P. W. Grocott

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