Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Originally published in Science Express on 15 March 2007
Science 13 April 2007:
Vol. 316. no. 5822, pp. 295 - 298
DOI: 10.1126/science.1139221
Prev | Table of Contents | Next

Reports

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

Rajita Pappu,1* Susan R. Schwab,2* Ivo Cornelissen,1 João P. Pereira,2 Jean B. Regard,1 Ying Xu,2 Eric Camerer,1 Yao-Wu Zheng,1 Yong Huang,3 Jason G. Cyster,2{dagger} Shaun R. Coughlin1{dagger}

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.

1 Cardiovascular Research Institute, University of California, San Francisco, 600 16th Street S472D, San Francisco, CA 94143–2240, USA.
2 Howard Hughes Medical Institute (HHMI) and Department of Microbiology and Immunology, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143–0414, USA.
3 Drug Studies Unit, Department of Biopharmaceutical Sciences, University of California, San Francisco, 296 Lawrence Street, South San Francisco, CA 94080, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: Shaun.Coughlin{at}ucsf.edu (S.R.C.); Jason.Cyster{at}ucsf.edu (J.G.C.)

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Immunosuppressive human anti-lymphocyte autoantibodies specific for the type 1 sphingosine 1-phosphate receptor.
J.-J. Liao, M.-C. Huang, K. Fast, K. Gundling, M. Yadav, J. R. Van Brocklyn, M. R. Wabl, and E. J. Goetzl (2009)
FASEB J 23, 1786-1796
   Abstract »    Full Text »    PDF »
Sphingosine-1-Phosphate: A Novel Nonhypoxic Activator of Hypoxia-Inducible Factor-1 in Vascular Cells.
M. D. Michaud, G. A. Robitaille, J.-P. Gratton, and D. E. Richard (2009)
Arterioscler. Thromb. Vasc. Biol. 29, 902-908
   Abstract »    Full Text »    PDF »
Sphingosine kinase regulation and cardioprotection.
J. S. Karliner (2009)
Cardiovasc Res 82, 184-192
   Abstract »    Full Text »    PDF »
Sphingosine-1-phosphate as a mediator of high-density lipoprotein effects in cardiovascular protection.
K. Sattler and B. Levkau (2009)
Cardiovasc Res 82, 201-211
   Abstract »    Full Text »    PDF »
Sphingosine-1-phosphate and modulation of vascular tone.
J. Igarashi and T. Michel (2009)
Cardiovasc Res 82, 212-220
   Abstract »    Full Text »    PDF »
Regulation of vascular physiology and pathology by the S1P2 receptor subtype.
A. Skoura and T. Hla (2009)
Cardiovasc Res 82, 221-228
   Abstract »    Full Text »    PDF »
Thymic progenitor homing and lymphocyte homeostasis are linked via S1P-controlled expression of thymic P-selectin/CCL25.
K. Gossens, S. Naus, S. Y. Corbel, S. Lin, F. M.V. Rossi, J. Kast, and H. J. Ziltener (2009)
J. Exp. Med. 206, 761-778
   Abstract »    Full Text »    PDF »
Settling the thymus: immigration requirements.
J. G. Cyster (2009)
J. Exp. Med. 206, 731-734
   Abstract »    Full Text »    PDF »
Sphingosine-1-phosphate: the Swiss army knife of sphingolipid signaling.
M. Maceyka, S. Milstien, and S. Spiegel (2009)
J. Lipid Res. 50, S272-S276
   Abstract »    Full Text »    PDF »
Sphingosine 1-phosphate regulates regeneration and fibrosis after liver injury via sphingosine 1-phosphate receptor 2.
H. Ikeda, N. Watanabe, I. Ishii, T. Shimosawa, Y. Kume, T. Tomiya, Y. Inoue, T. Nishikawa, N. Ohtomo, Y. Tanoue, et al. (2009)
J. Lipid Res. 50, 556-564
   Abstract »    Full Text »    PDF »
Accumulation of Fingolimod (FTY720) in Lymphoid Tissues Contributes to Prolonged Efficacy.
S.-C. Sensken, C. Bode, and M. H. Graler (2009)
J. Pharmacol. Exp. Ther. 328, 963-969
   Abstract »    Full Text »    PDF »
Anti-Inflammatory Effects of Sphingosine Kinase Modulation in Inflammatory Arthritis.
W.-Q. Lai, A. W. Irwan, H. H. Goh, H. S. Howe, D. T. Yu, R. Valle-Onate, I. B. McInnes, A. J. Melendez, and B. P. Leung (2008)
J. Immunol. 181, 8010-8017
   Abstract »    Full Text »    PDF »
HDL: bridging past and present with a look at the future.
A. M. Scanu and C. Edelstein (2008)
FASEB J 22, 4044-4054
   Abstract »    Full Text »    PDF »
Sphingolipids in the Lungs.
S. Uhlig and E. Gulbins (2008)
Am. J. Respir. Crit. Care Med. 178, 1100-1114
   Abstract »    Full Text »    PDF »
Induction of Antiproliferative Connective Tissue Growth Factor Expression in Wilms' Tumor Cells by Sphingosine-1-Phosphate Receptor 2.
M.-H. Li, T. Sanchez, A. Pappalardo, K. R. Lynch, T. Hla, and F. Ferrer (2008)
Mol. Cancer Res. 6, 1649-1656
   Abstract »    Full Text »    PDF »
Lysophospholipid signaling in the function and pathology of the reproductive system.
X. Ye (2008)
Hum. Reprod. Update 14, 519-536
   Abstract »    Full Text »    PDF »
Thymic Emigration: When and How T Cells Leave Home.
M. A. Weinreich and K. A. Hogquist (2008)
J. Immunol. 181, 2265-2270
   Abstract »    Full Text »    PDF »
Sphingosine kinase 1/S1P receptor signaling axis controls glial proliferation in mice with Sandhoff disease.
Y.-P. Wu, K. Mizugishi, M. Bektas, R. Sandhoff, and R. L. Proia (2008)
Hum. Mol. Genet. 17, 2257-2264
   Abstract »    Full Text »    PDF »
Plasma sphingosine-1-phosphate measurement in healthy subjects: close correlation with red blood cell parameters.
R. Ohkawa, K. Nakamura, S. Okubo, S. Hosogaya, Y. Ozaki, M. Tozuka, N. Osima, H. Yokota, H. Ikeda, and Y. Yatomi (2008)
Ann Clin Biochem 45, 356-363
   Abstract »    Full Text »    PDF »
"Inside-Out" Signaling of Sphingosine-1-Phosphate: Therapeutic Targets.
K. Takabe, S. W. Paugh, S. Milstien, and S. Spiegel (2008)
Pharmacol. Rev. 60, 181-195
   Abstract »    Full Text »    PDF »
Sphingosine 1-Phosphate Regulates the Egress of IgA Plasmablasts from Peyer's Patches for Intestinal IgA Responses.
M. Gohda, J. Kunisawa, F. Miura, Y. Kagiyama, Y. Kurashima, M. Higuchi, I. Ishikawa, I. Ogahara, and H. Kiyono (2008)
J. Immunol. 180, 5335-5343
   Abstract »    Full Text »    PDF »
The Enigma of Sphingosine 1-Phosphate Synthesis: A Novel Role for Endothelial Sphingosine Kinases.
J. Igarashi and T. Michel (2008)
Circ. Res. 102, 630-632
   Full Text »    PDF »
Vascular Endothelium As a Contributor of Plasma Sphingosine 1-Phosphate.
K. Venkataraman, Y.-M. Lee, J. Michaud, S. Thangada, Y. Ai, H. L. Bonkovsky, N. S. Parikh, C. Habrukowich, and T. Hla (2008)
Circ. Res. 102, 669-676
   Abstract »    Full Text »    PDF »
S1P1 receptor expression regulates emergence of NKT cells in peripheral tissues.
M. L. Allende, D. Zhou, D. N. Kalkofen, S. Benhamed, G. Tuymetova, C. Borowski, A. Bendelac, and R. L. Proia (2008)
FASEB J 22, 307-315
   Abstract »    Full Text »    PDF »
Isoflurane mediates protection from renal ischemia-reperfusion injury via sphingosine kinase and sphingosine-1-phosphate-dependent pathways.
M. Kim, M. Kim, N. Kim, V. D. D'Agati, C. W. Emala Sr, and H. T. Lee (2007)
Am J Physiol Renal Physiol 293, F1827-F1835
   Abstract »    Full Text »    PDF »
HDL serves as a S1P signaling platform mediating a multitude of cardiovascular effects.
K. M. Argraves and W. S. Argraves (2007)
J. Lipid Res. 48, 2325-2333
   Abstract »    Full Text »    PDF »
Cutting Edge: Modulation of Intestinal Autoimmunity and IL-2 Signaling by Sphingosine Kinase 2 Independent of Sphingosine 1-Phosphate.
E. T. Samy, C. A. Meyer, P. Caplazi, C. L. Langrish, J. M. Lora, H. Bluethmann, and S. L. Peng (2007)
J. Immunol. 179, 5644-5648
   Abstract »    Full Text »    PDF »
Preferential Sphingosine-1-Phosphate Enrichment and Sphingomyelin Depletion Are Key Features of Small Dense HDL3 Particles: Relevance to Antiapoptotic and Antioxidative Activities.
A. Kontush, P. Therond, A. Zerrad, M. Couturier, A. Negre-Salvayre, J. A. de Souza, S. Chantepie, and M. J. Chapman (2007)
Arterioscler. Thromb. Vasc. Biol. 27, 1843-1849
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)