Journal
FASEB JOURNAL
Volume 27, Issue 3, Pages 1001-1011Publisher
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.12-219618
Keywords
sphingosine-1-phosphate; lymphocytes
Categories
Funding
- U.S. National Institutes of Health (NIH) [R37-GM043880, U19-AI077435, K12-HD055881]
- Cure Research Foundation [KG090510]
- NIH [T32HL094290, P30CA16059]
- Japan Society for the Promotion of Science Postdoctoral Fellow
- National Institute of Neurological Disorders and Stroke Center Core [5P30NS047463]
Ask authors/readers for more resources
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, Spns(2-/-) 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 Spns(2-/-) mice as well as in specific tissues, including lymph nodes, and interstitial fluid. Moreover, lymph nodes from Spns(2-/-) 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
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available