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Erythrocytes serve as a reservoir for cellular and extracellular sphingosine 1‐phosphate
Author(s) -
Bode Constantin,
Sensken SvenChristian,
Peest Ulrike,
Beutel Gernot,
Thol Felicitas,
Levkau Bodo,
Li Zaiguo,
Bittman Robert,
Huang Tao,
Tölle Markus,
van der Giet Markus,
Gräler Markus H.
Publication year - 2010
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.22507
Subject(s) - sphingosine 1 phosphate , transcellular , sphingosine , extracellular , microbiology and biotechnology , sphingosine 1 phosphate receptor , red blood cell , chemistry , biochemistry , albumin , receptor , biology , biophysics
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. J. Cell. Biochem. 109: 1232–1243, 2010. © 2010 Wiley‐Liss, Inc.