Abstract
Although the distribution of cellular membrane phospholipid composition is well characterised in human erythrocytes, in-vivo turnover and dynamic flux of phospholipids between plasma and erythrocytes in physiological and in particular during disease states are mostly unknown. Erythrocyte mass primarily consisted of lipids and phosphatidylcholine (PC) contributes to the significant proportion of phospholipid membrane composition. Esterified membrane PC can be utilised during pathological processes to generate pro and anti-inflammatory lipid mediators, which can contribute to the pathogenesis of acute respiratory distress syndrome (ARDS). In this study, utilising isotope labelling of choline and analytical methods with electrospray mass spectrometry (ESI-MS/MS), we characterised individual molecular composition and dynamic exchange of PC, sphingomyelins (SM) and lysophosphatidylcholines (LPC) between plasma and erythrocytes. In ARDS patients, there were significant alterations in PC molecular composition, coupled with a continuous loss of arachidonoyl-PC species over time. Infusion of methyl-D9-choline chloride resulted in enrichment of labelled choline into plasma PC and LPC via CDP-choline pathway with subsequent incorporation into erythrocyte PC. As expected, erythrocyte methyl-D9 PC enrichment is much slower than plasma. Patients had much faster and higher fractional enrichment of all PC and LPC molecules suggesting increased flux between plasma and erythrocytes. There was a particular pattern of incorporation, where the arachidonoyl-PC species achieved equilibrium with plasma rapidly and retained highest concentrations of enrichment compared to the other PC species. Increased enrichment of arachidonoyl-PC coupled with virtually no increase or depletion of its concentrations suggests the possibility of substrate donation for other cell types for the participation of eicosanoid biosynthesis during inflammatory conditions like ARDS. In summary, this study revealed an alerted pattern erythrocyte molecular phospholipid composition and flux in patients with acute respiratory distress syndrome and the pathological consequences of these changes needs further exploration.
Highlights
Mammalian cell membranes consist of a mixture of glycerophospholipids and proteins
Except for erythrocytes, synthesis de novo via the cytidine diphosphate (CDP)-choline pathway with sequential acyl-remodelling of fatty acids moieties by phospholipases and acyltransferases defines the final membrane PC composition in all mammalian cells [4]
Erythrocytes maintain a distinct distribution of phospholipid composition compared to plasma
Summary
Mammalian cell membranes consist of a mixture of glycerophospholipids and proteins. Relative molecular composition of membrane phospholipids can vary between cells and primarily depends on the specific cellular function. In addition to the structural role, membrane phospholipids are involved in cellular regulatory mechanisms [2]. Characteristics of membrane phospholipid composition and their dynamic turnover during various disease states define the cell’s ability to execute many immunological functions and intracellular signal transduction, maintenance of cellular membrane integrity and cell survival [2, 3]. Except for erythrocytes, synthesis de novo via the CDP-choline pathway with sequential acyl-remodelling of fatty acids moieties by phospholipases and acyltransferases defines the final membrane PC composition in all mammalian cells [4]
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