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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 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.

Pubmed ID: 17363629

Authors

  • Pappu R
  • Schwab SR
  • Cornelissen I
  • Pereira JP
  • Regard JB
  • Xu Y
  • Camerer E
  • Zheng YW
  • Huang Y
  • Cyster JG
  • Coughlin SR

Journal

Science (New York, N.Y.)

Publication Data

April 13, 2007

Associated Grants

  • Agency: NHLBI NIH HHS, Id: HL07731
  • Agency: NHLBI NIH HHS, Id: R01 HL065590

Mesh Terms

  • Animals
  • Bone Marrow
  • Chemotaxis, Leukocyte
  • Chromatography, Liquid
  • Endothelium, Vascular
  • Female
  • Hematopoietic Stem Cells
  • Lymphocytes
  • Lysophospholipids
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Phosphotransferases (Alcohol Group Acceptor)
  • Receptors, Lysosphingolipid
  • Sphingosine
  • Tandem Mass Spectrometry