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Sphingosine 1-phosphate has a negative effect on RBC storage quality
Ariel Hay1, Travis Nemkov2, Fabia Gamboni2
1Department of Pathology, University of Virginia, Charlottesville, VA.
Blood Advances
|December 5, 2022
Summary
Supplementing stored red blood cells with sphingosine-1-phosphate (S1P) boosts energy metabolism but paradoxically reduces post-transfusion recovery. This effect was reversed in Sphk1 knockout mice and under hypoxic storage conditions.
Area of Science:
- Hematology
- Biochemistry
- Cell Biology
Background:
- Blood storage depletes critical red blood cell (RBC) metabolites like adenosine triphosphate (ATP) and 2,3-diphosphoglycerate (DPG).
- These metabolites regulate RBC function, oxygen transport, and survival after transfusion.
- Sphingosine-1-phosphate (S1P) is known to influence glycolytic pathways.
Purpose of the Study:
- To investigate the effect of S1P supplementation on RBC energy metabolism during storage.
- To determine if S1P supplementation improves post-transfusion recovery of RBCs.
- To explore the role of S1P in RBCs from different mouse strains and under various storage conditions.
Main Methods:
- Quantified S1P levels in stored human RBC samples.
- Supplemented human and murine RBCs with S1P and analyzed metabolism and post-transfusion recovery.
- Utilized metabolomics, isotopic tracing (1,2,3-13C3-glucose), proteomics, and Sphk1 knockout mouse models.
- Investigated effects under normoxic and hypoxic storage conditions.
Main Results:
- Stored RBCs showed decreased S1P levels, with higher levels in units from female or older donors.
- S1P supplementation increased glycolytic metabolites (ATP, DPG) but decreased pentose phosphate pathway activity.
- Contrary to hypothesis, S1P supplementation led to lower post-transfusion recovery in murine models.
- These effects were reversed in Sphk1 knockout mice and under hypoxic storage.
Conclusions:
- S1P enhances RBC energy metabolism during storage.
- S1P acts as a negative regulator of antioxidant metabolism in stored RBCs.
- S1P supplementation negatively impacts RBC post-transfusion recovery, likely due to altered metabolic balance.
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