Erythrocytes serve as a reservoir for cellular and extracellular sphingosine 1‐phosphate |
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Authors: | Constantin Bode Sven‐Christian Sensken Ulrike Peest Gernot Beutel Felicitas Thol Bodo Levkau Zaiguo Li Robert Bittman Tao Huang Markus Tölle Markus van der Giet Markus H. Gräler |
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Affiliation: | 1. Institute for Immunology, Hannover Medical School, Carl‐Neuberg‐Str. 1, 30625 Hanover, Germany;2. Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Carl‐Neuberg‐Str. 1, 30625 Hanover, Germany;3. Institute of Pathophysiology, University Hospital Essen, Hufelandstrasse 55, 45122 Essen, Germany;4. Department of Chemistry and Biochemistry, Queens College of City University of New York, Flushing, New York 11367‐1597;5. Department of Nephrology, Charité‐Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany |
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Abstract: | Sphingosine 1‐phosphate (S1P) in blood is phosphorylated, stored, and transported by red blood cells (RBC). Release of S1P from RBC into plasma is a regulated process that does not occur in plasma‐ or serum‐free media. Plasma fractionation and incubations with isolated and recombinant proteins identified high density lipoprotein (HDL) and serum albumin (SA) as non‐redundant endogenous triggers for S1P release from RBC. S1P bound to SA and HDL was able to stimulate the S1P1 receptor in calcium flux experiments. The binding capability of acceptor molecules triggers S1P release, as demonstrated with the anti‐S1P antibody Sphingomab?. More S1P was extracted from RBC membranes by HDL than by SA. Blood samples from anemic patients confirmed a reduced capacity for S1P release in plasma. In co‐cultures of RBC and endothelial cells (EC), we observed transcellular transportation of S1P as a second function of RBC‐associated S1P in the absence of SA and HDL and during tight RBC‐EC contact, mimicking conditions in tissue interstitium and capillaries. In contrast to S1P bound to SA and HDL, RBC‐associated S1P was significantly incorporated by EC after S1P lyase (SGPL1) inhibition. RBC‐associated S1P, therefore, has two functions: (1) It contributes to the cellular pool of SGPL1‐sensitive S1P in tissues after transcellular transportation and (2) it helps maintain extracellular S1P levels via SA and HDL independently from SGPL1 activity. J. Cell. Biochem. 109: 1232–1243, 2010. © 2010 Wiley‐Liss, Inc. |
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Keywords: | apolipoprotein serum albumin scramblase S1P lyase plasma |
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