title: Erythrocytes serve as a reservoir for cellular and extracellular sphingosine 1-phosphate.
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 S1P(1) 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.
authors.affiliation: Institute for Immunology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hanover, Germany.
authors.forename: Constantin
authors.initials: C
authors.lastname: Bode
authors.forename: Sven-Christian
authors.initials: SC
authors.lastname: Sensken
authors.forename: Ulrike
authors.initials: U
authors.lastname: Peest
authors.forename: Gernot
authors.initials: G
authors.lastname: Beutel
authors.forename: Felicitas
authors.initials: F
authors.lastname: Thol
authors.forename: Bodo
authors.initials: B
authors.lastname: Levkau
authors.forename: Zaiguo
authors.initials: Z
authors.lastname: Li
authors.forename: Robert
authors.initials: R
authors.lastname: Bittman
authors.forename: Tao
authors.initials: T
authors.lastname: Huang
authors.forename: Markus
authors.initials: M
authors.lastname: Tölle
authors.forename: Markus
authors.initials: M
authors.lastname: van der Giet
authors.forename: Markus H
authors.initials: MH
authors.lastname: Gräler
mesh_terms: D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008075:Lipoproteins, HDL / Q000494:pharmacology; D008246:Lysophospholipids / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D012709:Serum Albumin / Q000494:pharmacology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism; D053719:Tandem Mass Spectrometry
chemical_list: D008075:Lipoproteins, HDL; D008246:Lysophospholipids; D012709:Serum Albumin; C060506:sphingosine 1-phosphate; D013110:Sphingosine