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Insight into erythrocyte phospholipid molecular flux in healthy humans and in patients with acute respiratory distress syndrome

Insight into erythrocyte phospholipid molecular flux in healthy humans and in patients with acute respiratory distress syndrome
Insight into erythrocyte phospholipid molecular flux in healthy humans and in patients with acute respiratory distress syndrome

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 lysopho-sphatidylcholines (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.

1932-6203
Dushianthan, Ahilanandan
013692a2-cf26-4278-80bd-9d8fcdb17751
Cusack, Rebecca
dfb1595f-2792-4f76-ac6d-da027cf40146
Koster, Grielof
e404c38a-6f48-430a-adf0-5208228cb9e7
Grocott, Michael P.W.
1e87b741-513e-4a22-be13-0f7bb344e8c2
Postle, Anthony D.
0fa17988-b4a0-4cdc-819a-9ae15c5dad66
Dushianthan, Ahilanandan
013692a2-cf26-4278-80bd-9d8fcdb17751
Cusack, Rebecca
dfb1595f-2792-4f76-ac6d-da027cf40146
Koster, Grielof
e404c38a-6f48-430a-adf0-5208228cb9e7
Grocott, Michael P.W.
1e87b741-513e-4a22-be13-0f7bb344e8c2
Postle, Anthony D.
0fa17988-b4a0-4cdc-819a-9ae15c5dad66

Dushianthan, Ahilanandan, Cusack, Rebecca, Koster, Grielof, Grocott, Michael P.W. and Postle, Anthony D. (2019) Insight into erythrocyte phospholipid molecular flux in healthy humans and in patients with acute respiratory distress syndrome. PLoS ONE, 14 (8), [e0221595]. (doi:10.1371/journal.pone.0221595).

Record type: Article

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 lysopho-sphatidylcholines (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.

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Accepted/In Press date: 10 August 2019
Published date: 27 August 2019

Identifiers

Local EPrints ID: 434202
URI: http://eprints.soton.ac.uk/id/eprint/434202
ISSN: 1932-6203
PURE UUID: c4cd09b6-6541-4388-937d-d20d69645233
ORCID for Ahilanandan Dushianthan: ORCID iD orcid.org/0000-0002-0165-3359
ORCID for Michael P.W. Grocott: ORCID iD orcid.org/0000-0002-9484-7581
ORCID for Anthony D. Postle: ORCID iD orcid.org/0000-0001-7361-0756

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Date deposited: 16 Sep 2019 16:30
Last modified: 07 Oct 2020 02:21

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Contributors

Author: Ahilanandan Dushianthan ORCID iD
Author: Rebecca Cusack
Author: Grielof Koster

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