Promotion of Lymphocyte Egress into Blood and Lymph by Distinct Sources of Sphingosine-1-Phosphate

Lymphocytes require sphingosine-1-phosphate (S1P) receptor-1 to exit lymphoid organs, but the source(s) of extracellular S1P and whether S1P directly promotes egress are unknown. By using mice in which the two kinases that generate S1P were conditionally ablated, we find that plasma S1P is mainly he...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2007-04, Vol.316 (5822), p.295-298
Main Authors: Pappu, Rajita, Schwab, Susan R, Cornelissen, Ivo, Pereira, João P, Regard, Jean B, Xu, Ying, Camerer, Eric, Zheng, Yao-Wu, Huang, Yong, Cyster, Jason G, Coughlin, Shaun R
Format: Article
Language:English
Subjects:
Animals
B lymphocytes
Biological and medical sciences
Blood
Blood plasma
Blood transfusion
Bone Marrow - metabolism
Chemotaxis, Leukocyte - physiology
Chromatography, Liquid
Endothelium, Vascular
Female
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Genetics of the immune response
Hematopoietic Stem Cells - metabolism
Immune system
Immunobiology
Kinases
Lymph
Lymph nodes
Lymphocytes
Lymphocytes - metabolism
Lymphocytes - physiology
Lysophospholipids - biosynthesis
Lysophospholipids - blood
Lysophospholipids - deficiency
Lysophospholipids - physiology
Male
Mice
Mice, Inbred C57BL
Phosphates
Phosphotransferases (Alcohol Group Acceptor) - genetics
Phosphotransferases (Alcohol Group Acceptor) - metabolism
Receptors, Lysosphingolipid - physiology
Rodents
Signal transduction
Sphingosine - analogs & derivatives
Sphingosine - biosynthesis
Sphingosine - blood
Sphingosine - deficiency
Sphingosine - physiology
Spleen
T lymphocytes
Tandem Mass Spectrometry
Thymocytes
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Summary:Lymphocytes require sphingosine-1-phosphate (S1P) receptor-1 to exit lymphoid organs, but the source(s) of extracellular S1P and whether S1P directly promotes egress are unknown. By using mice in which the two kinases that generate S1P were conditionally ablated, we find that plasma S1P is mainly hematopoietic in origin, with erythrocytes a major contributor, whereas lymph S1P is from a distinct radiation-resistant source. Lymphocyte egress from thymus and secondary lymphoid organs was markedly reduced in kinase-deficient mice. Restoration of S1P to plasma rescued egress to blood but not lymph, and the rescue required lymphocyte expression of S1P-receptor-1. Thus, separate sources provide S1P to plasma and lymph to help lymphocytes exit the low-S1P environment of lymphoid organs. Disruption of compartmentalized S1P signaling is a plausible mechanism by which S1P-receptor-1 agonists function as immunosuppressives.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1139221