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

在德国，呼吸系统疾病导致的死亡占记录死亡人数的12%以上。由严重急性呼吸综合征冠状病毒-2(SARS-CoV-2)引起的冠状病毒病-2019年(新冠肺炎)也对一些非常严重的肺损伤负责。新冠肺炎疫情清楚地表明，当面临大量需要重症监护并同时依赖人工呼吸机的患者时，卫生系统是多么脆弱。因此，避免需要人工通风的可能性不仅对有关患者是可取的，而且对整个卫生系统也是可取的。脂质信号分子1-磷酸鞘氨醇(S1P)形成并储存在红细胞(RBC)中，参与对低氧条件的适应。我们能够证明S1P也积聚在严重新冠肺炎患者的红细胞中，并且它可能参与了向糖酵解和2，3-二磷酸甘油酸合成的代谢转变。这导致了一种假设，即RBC中的细胞内S1P可能有助于呼吸系统疾病对低氧条件的适应性反应，这一假设尚未被研究。为了验证这一假说，在第一步，我们将研究S1P调节RBC供氧的生化机制，以便寻找RBC预适应促进氧释放的医学上可用的可能性。在这种情况下，血液抗原对红细胞适应能力的影响也将被调查，因为几项研究表明，A型血的患者更喜欢严重的新冠肺炎病程。最后，生化结果也将在新冠肺炎患者和急慢性呼吸道疾病患者中得到验证。该项目的研究结果理想地可以为严重呼吸道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.