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

在德国，有记录的死亡人数中，呼吸系统疾病占12%以上。由严重急性呼吸系统综合征冠状病毒-2 （SARS-CoV-2）引起的冠状病毒病-2019 （COVID-19）也会导致一些非常严重的肺损伤。COVID-19大流行清楚地表明，当面对大量需要重症监护的患者同时依赖人工通气时，卫生系统是多么脆弱。因此，避免需要人工通气的可能性不仅对有关患者，而且对整个卫生系统都是可取的。脂质信号分子鞘氨醇1-磷酸（S1P）在红细胞（RBC）中形成并储存，并参与对缺氧条件的适应。我们能够证明S1P也在严重的COVID-19患者的红细胞中积累，并且它可能参与糖酵解和2,3-双磷酸甘油酸合成增强的代谢转变。这导致了一种假说，即红细胞中的细胞内S1P可能有助于呼吸系统疾病对缺氧条件的适应性反应，这一假说尚未得到研究。为了验证这一假设，在第一步，我们将研究s1p调节红细胞供氧的生化机制，然后寻找红细胞预处理促进氧气释放的医学上可用的可能性。在这种情况下，血液抗原对RBC适应能力的影响也将被研究，因为一些研究表明a血型患者更倾向于COVID-19疾病的严重病程。最后，还将在COVID-19患者和急慢性呼吸道疾病患者中验证生化结果。这个项目的研究结果可能会为严重呼吸系统疾病的治疗带来新的预防和治疗可能性。

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.