Sphingosine 1-phosphate (S1P) mediated adaptations to hypoxemic conditions in red blood cells (RBC) in acute and chronic respiratory diseases

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Respiratory diseases contribute to more than 12% of documented deaths in Germany. The coronavirus disease-2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is also responsible for some very heavy pulmonary damage. The COVID-19 pandemic has made clear how vulnerable the health system is when faced with a large number of patients requiring intensive care who depend on artificial ventilation at the same time. Possibilities to avoid the need for artificial ventilation are therefore desirable not only for the patients concerned, but also for the health system as a whole. The lipid signaling molecule sphingosine 1-phosphate (S1P) is formed and stored in red blood cells (RBC) and is involved in the adaptation to hypoxic conditions. We were able to show that S1P also accumulated in RBC of severe COVID-19 patients, and that it may be involved in a metabolic shift towards enhanced glycolysis and 2,3-bisphosphoglycerate synthesis. This leads to the hypothesis that intracellular S1P in RBC could contribute to an adaptive response to hypoxic conditions in respiratory diseases, which has not yet been investigated. To test this hypothesis, in a first step, the biochemical mechanisms of S1P-modulated oxygen supply by RBC will be examined in order to then search for medically usable possibilities of preconditioning of RBC to promote oxygen release. In this context, the influence of blood antigens on the adaptation capabilities of RBC will also be investigated, as several studies have shown a preference of patients with blood group A to a serious course of COVID-19 disease. Finally, biochemical findings will also be verified in COVID-19 patients and patients with acute and chronic respiratory diseases. The findings of this project could ideally lead to new preventive and therapeutic possibilities for the treatment of serious respiratory diseases.