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

1-磷酸鞘氨醇 (S1P) 介导急性和慢性呼吸道疾病中红细胞 (RBC) 对低氧血症的适应

• 批准号: 504972615
• 负责人: Professor Dr. Markus Gräler, Ph.D.
• 金额: --
• 依托单位: Klinik für Anästhesiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/504972615?language=en
• 关键词: Sphingosine; phosphate; S1P; mediated; adaptations

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.

呼吸道疾病在德国有效的死亡人数中有12％以上。严重的急性呼吸综合症冠状病毒-2（SARS-COV-2）引起的冠状病毒疾病2019年（COVID-19）也造成了一些非常重的肺部损伤。当面对大量需要重症监护的患者时，COVID-19大流行已经明确了卫生系统的脆弱性，这些患者同时依靠人工通风。因此，避免需要人工通气的可能性不仅对有关患者，而且对于整个卫生系统都是可取的。脂质信号传导分子1-磷酸（S1P）形成并储存在红细胞（RBC）中，并参与对低氧条件的适应。我们能够证明S1P也积累在严重的CoVID-19患者的RBC中，并且可能与代谢转向增强的糖酵解和2,3-双磷酸甘油酸合成。这导致了这样的假设，即RBC中的细胞内S1P可能有助于对呼吸道疾病中缺氧条件的适应性反应，尚未研究。为了检验这一假设，将检查RBC的S1P调节氧气供应的生化机制，以便搜索RBC预处理的医学可用可能性，以促进氧气释放。在这种情况下，还将研究血液抗原对RBC适应能力的影响，因为几项研究表明，血管A组患者偏爱与Covid-199疾病的严重过程。最后，在199名患者和急性和慢性呼吸道疾病的患者中，还将验证生化发现。理想情况下，该项目的发现可以为治疗严重呼吸系统疾病的新预防和治疗可能性。