Abstract
Sphingosine-1-phosphate (S1P) is a bioactive lipid implicated in e.g. angiogenesis, lymphocyte trafficking, and endothelial barrier function. Erythrocytes are a main source of plasma S1P together with platelets and endothelial cells. Apolipoprotein M (apoM) in HDL carries 70% of plasma S1P, whereas 30% is carried by albumin. The current aim was to investigate the role of apoM in export of S1P from human erythrocytes. Erythrocytes exported S1P more efficiently to HDL than to albumin, particularly when apoM was present in HDL. In contrast, export of sphingosine to HDL was unaffected by the presence of apoM. The specific ability of apoM to promote export of S1P was independent of apoM being bound in HDL particles. Treatment with MK-571, an inhibitor of the ABCC1 transporter, effectively reduced export of S1P from human erythrocytes to apoM, whereas the export was unaffected by inhibitors of ABCB1 or ATPase. Thus, ABCC1 could be involved in export of S1P from erythrocytes to apoM.
Highlights
Sphingosine-1-phosphate (S1P) is a small bioactive lipid and a ligand for five G-protein-coupled receptors (S1P1-S1P5) regulating multiple biological actions
In order to investigate the effects of Apolipoprotein M (apoM) in human HDL on export of S1P from human erythrocytes, we developed an affinity column where monoclonal antibodies specific for human apoM were generated and coupled to a resin column
The present data suggest that HDL promotes export of S1P from human erythrocytes compared to albumin and that this is further enhanced when apoM is present in the HDL particles
Summary
Sphingosine-1-phosphate (S1P) is a small bioactive lipid and a ligand for five G-protein-coupled receptors (S1P1-S1P5) regulating multiple biological actions. Bone-marrow derived cells, hepatocytes, endothelial cells, platelets, and erythrocytes express Sphk[1] or Spkh[2] and are potential contributors of plasma S1P2,5,8,9. A conditional knockout mouse with lack of both sphk[1] and sphk[25] and undetectable plasma S1P regain normal plasma S1P levels after bone marrow transplantation with cells from a WT mouse[5]. Transplantation of bone marrow from sphk1−/−sphk2+/− mice (with 65% reduced plasma S1P) into WT mice did not reduce plasma S1P9 This suggests that non-hematopoietic cells, presumably endothelial cells, can maintain plasma S1P levels. Plasma levels of S1P correlate with the hematocrit[11] and are decreased in patients with anemia[12], suggesting that erythrocytes contribute to plasma S1P. It is unknown whether and how erythrocyte-produced S1P is transferred to apoM
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