Erythrocytes increase endogenous sphingosine 1-phosphate levels as an adaptive response to SARS-CoV-2 infection. Issue 24 (22nd December 2021)

• Record Type: Journal Article
• Authors: Winkler, Martin Sebastian; Claus, Ralf Alexander; Schilder, Mareike; Pöhlmann, Stefan; Coldewey, Sina M.; Grundmann, Julian; Fricke, Torben; Moerer, Onnen; Meissner, Konrad; Bauer, Michael; Hofmann-Winkler, Heike; Gräler, Markus H.
• Is Part Of: Clinical science. Volume 135:Issue 24(2021)
• Page Start: 2781
• Page End: 2791
• Publication Date: 2021-12-22
• Subjects: endothelial cell barrier -- erythrocytes -- high-density lipoprotein -- hypoxia -- infection -- SARS-CoV-2; Medicine -- Periodicals; Biochemistry -- Periodicals; 616
• DOI: 10.1042/CS20210666
• Languages: English
• ISSNs: 0143-5221

Abstract

Abstract: Low plasma levels of the signaling lipid metabolite sphingosine 1-phosphate (S1P) are associated with disrupted endothelial cell (EC) barriers, lymphopenia and reduced responsivity to hypoxia. Total S1P levels were also reduced in 23 critically ill patients with coronavirus disease 2019 (COVID-19), and the two main S1P carriers, serum albumin (SA) and high-density lipoprotein (HDL) were dramatically low. Surprisingly, we observed a carrier-changing shift from SA to HDL, which probably prevented an even further drop in S1P levels. Furthermore, intracellular S1P levels in red blood cells (RBCs) were significantly increased in COVID-19 patients compared with healthy controls due to up-regulation of S1P producing sphingosine kinase 1 and down-regulation of S1P degrading lyase expression. Cell culture experiments supported increased sphingosine kinase activity and unchanged S1P release from RBC stores of COVID-19 patients. These observations suggest adaptive mechanisms for maintenance of the vasculature and immunity as well as prevention of tissue hypoxia in COVID-19 patients.