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Spns2, a transporter of phosphorylated sphingoid bases, regulates their blood and lymph levels, and the lymphatic network
Author(s) -
Nagahashi Masayuki,
Kim Eugene Y.,
Yamada Akimitsu,
Ramachandran Subramaniam,
Allegood Jeremy C.,
Hait Nitai C.,
Maceyka Michael,
Milstien Sheldon,
Takabe Kazuaki,
Spiegel Sarah
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.12-219618
Subject(s) - lymph , lymphatic system , transporter , phosphorylation , chemistry , microbiology and biotechnology , biochemistry , biology , medicine , immunology , pathology , gene
Sphingosine‐1‐phosphate (S1P), a ligand for 5 specific receptors, is a potent lipid mediator that plays important roles in lymphocyte trafficking and immune responses. S1P is produced inside cells and therefore must be secreted to exert its effects through these receptors. Spinster 2 (Spns2) is one of the cell surface transporters thought to secrete S1P. We have shown that Spns2 can export endogenous S1P from cells and also dihydro‐S1P, which is active at all cell surface S1P receptors. Moreover, Spns2 –/– mice have decreased levels of both of these phosphorylated sphingoid bases in blood, accompanied by increases in very long chain ceramide species, and have defective lymphocyte trafficking. Surprisingly, levels of S1P and dihydro‐S1P were increased in lymph from Spns2 –/– mice as well as in specific tissues, including lymph nodes, and interstitial fluid. Moreover, lymph nodes from Spns2 –/– mice have aberrant lymphatic sinus that appeared collapsed, with reduced numbers of lymphocytes. Our data suggest that Spns2 is an S1P transporter in vivo that plays a role in regulation not only of blood S1P but also lymph node and lymph S1P levels and consequently influences lymphocyte trafficking and lymphatic vessel network organization.—Nagahashi, M., Kim, E. Y., Yamada, A., Ramachandran, S., Allegood, J. C., Hait, N. C., Maceyka, M., Milstien, S., Takabe, K., Spiegel, S. Spns2, a transporter of phosphorylated sphingoid bases, regulates their blood and lymph levels and the lymphatic network. FASEB J. 27, 1001–1011 (2013). www.fasebj.org