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.

Subscribe

Logo for

Science 316 (5822): 295-298

Copyright © 2007 by the American Association for the Advancement of Science

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}

Abstract: 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.)


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Dynamin 2-dependent endocytosis is required for sustained S1PR1 signaling.
T. Willinger, S. M. Ferguson, J. P. Pereira, P. De Camilli, and R. A. Flavell (2014)
J. Exp. Med. 211, 685-700
   Abstract »    Full Text »    PDF »
MyD88- and TRIF-Independent Induction of Type I Interferon Drives Naive B Cell Accumulation but Not Loss of Lymph Node Architecture in Lyme Disease.
C. J. Hastey, J. Ochoa, K. J. Olsen, S. W. Barthold, and N. Baumgarth (2014)
Infect. Immun. 82, 1548-1558
   Abstract »    Full Text »    PDF »
Integrin {alpha}9 on lymphatic endothelial cells regulates lymphocyte egress.
K. Ito, J. Morimoto, A. Kihara, Y. Matsui, D. Kurotaki, M. Kanayama, S. Simmons, M. Ishii, D. Sheppard, A. Takaoka, et al. (2014)
PNAS 111, 3080-3085
   Abstract »    Full Text »    PDF »
Hepatic Apolipoprotein M (ApoM) Overexpression Stimulates Formation of Larger ApoM/Sphingosine 1-Phosphate-enriched Plasma High Density Lipoprotein.
M. Liu, J. Seo, J. Allegood, X. Bi, X. Zhu, E. Boudyguina, A. K. Gebre, D. Avni, D. Shah, M. G. Sorci-Thomas, et al. (2014)
J. Biol. Chem. 289, 2801-2814
   Abstract »    Full Text »    PDF »
Mendelian Disorders of High-Density Lipoprotein Metabolism.
F. Oldoni, R. J. Sinke, and J. A. Kuivenhoven (2014)
Circ. Res. 114, 124-142
   Abstract »    Full Text »    PDF »
Sphingosine 1-phosphate signalling.
K. Mendelson, T. Evans, and T. Hla (2014)
Development 141, 5-9
   Abstract »    Full Text »    PDF »
Sphingosine Kinases Are Not Required for Inflammatory Responses in Macrophages.
Y. Xiong, H. J. Lee, B. Mariko, Y.-C. Lu, A. J. Dannenberg, A. S. Haka, F. R. Maxfield, E. Camerer, R. L. Proia, and T. Hla (2013)
J. Biol. Chem. 288, 32563-32573
   Abstract »    Full Text »    PDF »
Unraveling the complexities of the HDL lipidome.
A. Kontush, M. Lhomme, and M. J. Chapman (2013)
J. Lipid Res. 54, 2950-2963
   Abstract »    Full Text »    PDF »
Predictability of Peripheral Lymphocyte Reduction of Novel S1P1 Agonists by In Vitro GPCR Signaling Profile.
H. Xu, M. McElvain, M. Fiorino, B. Henkle, L. Sherman, Y. Xu, E. Tominey, K. Kelley, M. Adlam, R. Burli, et al. (2013)
J Biomol Screen 18, 997-1007
   Abstract »    Full Text »    PDF »
Sphingosine kinase 2 (Sphk2) regulates platelet biogenesis by providing intracellular sphingosine 1-phosphate (S1P).
L. Zhang, N. Urtz, F. Gaertner, K. R. Legate, T. Petzold, M. Lorenz, A. Mazharian, S. P. Watson, and S. Massberg (2013)
Blood 122, 791-802
   Abstract »    Full Text »    PDF »
Critical role of sphingosine-1-phosphate receptor 2 (S1PR2) in acute vascular inflammation.
G. Zhang, L. Yang, G. S. Kim, K. Ryan, S. Lu, R. K. O'Donnell, K. Spokes, N. Shapiro, W. C. Aird, M. J. Kluk, et al. (2013)
Blood 122, 443-455
   Abstract »    Full Text »    PDF »
5'-AMP impacts lymphocyte recirculation through activation of A2B receptors.
H. R. Bouma, J. N. Mandl, A. M. Strijkstra, A. S. Boerema, J.-W. Kok, A. van Dam, A. IJzerman, F. G. M. Kroese, and R. H. Henning (2013)
J. Leukoc. Biol. 94, 89-98
   Abstract »    Full Text »    PDF »
S1P1 localizes to the colonic vasculature in ulcerative colitis and maintains blood vessel integrity.
D. C. Montrose, E. J. Scherl, B. P. Bosworth, X. K. Zhou, B. Jung, A. J. Dannenberg, and T. Hla (2013)
J. Lipid Res. 54, 843-851
   Abstract »    Full Text »    PDF »
Spns2, a transporter of phosphorylated sphingoid bases, regulates their blood and lymph levels, and the lymphatic network.
M. Nagahashi, E. Y. Kim, A. Yamada, S. Ramachandran, J. C. Allegood, N. C. Hait, M. Maceyka, S. Milstien, K. Takabe, and S. Spiegel (2013)
FASEB J 27, 1001-1011
   Abstract »    Full Text »    PDF »
Sphingosine 1-Phosphate Receptor Signaling Regulates Proper Embryonic Vascular Patterning.
K. Mendelson, T. Zygmunt, J. Torres-Vazquez, T. Evans, and T. Hla (2013)
J. Biol. Chem. 288, 2143-2156
   Abstract »    Full Text »    PDF »
S1P1 expression is controlled by the pro-oxidant activity of p66Shc and is impaired in B-CLL patients with unfavorable prognosis.
N. Capitani, L. Patrussi, L. Trentin, O. M. Lucherini, E. Cannizzaro, E. Migliaccio, F. Frezzato, C. Gattazzo, F. Forconi, P. Pelicci, et al. (2012)
Blood 120, 4391-4399
   Abstract »    Full Text »    PDF »
A novel role of sphingosine 1-phosphate receptor S1pr1 in mouse thrombopoiesis.
L. Zhang, M. Orban, M. Lorenz, V. Barocke, D. Braun, N. Urtz, C. Schulz, M.-L. von Bruhl, A. Tirniceriu, F. Gaertner, et al. (2012)
J. Exp. Med. 209, 2165-2181
   Abstract »    Full Text »    PDF »
S1P1 inhibits sprouting angiogenesis during vascular development.
A. B. Shoham, G. Malkinson, S. Krief, Y. Shwartz, Y. Ely, N. Ferrara, K. Yaniv, and E. Zelzer (2012)
Development 139, 3859-3869
   Abstract »    Full Text »    PDF »
The functional roles of S1P in immunity.
Y. Hisano, T. Nishi, and A. Kawahara (2012)
J. Biochem. 152, 305-311
   Abstract »    Full Text »    PDF »
Expression of sphingosine 1-phosphate receptors in the rat dorsal root ganglia and defined single isolated sensory neurons.
J. S. Kays, C. Li, and G. D. Nicol (2012)
Physiol Genomics 44, 889-901
   Abstract »    Full Text »    PDF »
Sphingosine-1-Phosphate-Induced Airway Hyper-Reactivity in Rodents Is Mediated by the Sphingosine-1-Phosphate Type 3 Receptor.
A. Trifilieff and J. R. Fozard (2012)
J. Pharmacol. Exp. Ther. 342, 399-406
   Abstract »    Full Text »    PDF »
Chronic Alcohol Consumption Impairs Distribution and Compromises Circulation of B Cells in B16BL6 Melanoma-Bearing Mice.
H. Zhang, Z. Zhu, and G. G. Meadows (2012)
J. Immunol. 189, 1340-1348
   Abstract »    Full Text »    PDF »
The Role of Sphingosine-1-Phosphate Transporter Spns2 in Immune System Function.
A. Nijnik, S. Clare, C. Hale, J. Chen, C. Raisen, L. Mottram, M. Lucas, J. Estabel, E. Ryder, H. Adissu, et al. (2012)
J. Immunol. 189, 102-111
   Abstract »    Full Text »    PDF »
Gaucher disease gene GBA functions in immune regulation.
J. Liu, S. Halene, M. Yang, J. Iqbal, R. Yang, W. Z. Mehal, W.-L. Chuang, D. Jain, T. Yuen, L. Sun, et al. (2012)
PNAS 109, 10018-10023
   Abstract »    Full Text »    PDF »
Molecular features of hepatosplenic T-cell lymphoma unravels potential novel therapeutic targets.
M. Travert, Y. Huang, L. de Leval, N. Martin-Garcia, M.-H. Delfau-Larue, F. Berger, J. Bosq, J. Briere, J. Soulier, E. MacIntyre, et al. (2012)
Blood 119, 5795-5806
   Abstract »    Full Text »    PDF »
Expansion of Cortical and Medullary Sinuses Restrains Lymph Node Hypertrophy during Prolonged Inflammation.
K. W. Tan, K. P. Yeo, F. H. S. Wong, H. Y. Lim, K. L. Khoo, J.-P. Abastado, and V. Angeli (2012)
J. Immunol. 188, 4065-4080
   Abstract »    Full Text »    PDF »
Sphingosine 1-Phosphate (S1P) Regulates Glucose-stimulated Insulin Secretion in Pancreatic Beta Cells.
J. Cantrell Stanford, A. J. Morris, M. Sunkara, G. J. Popa, K. L. Larson, and S. Ozcan (2012)
J. Biol. Chem. 287, 13457-13464
   Abstract »    Full Text »    PDF »
S1P promotes murine progenitor cell egress and mobilization via S1P1-mediated ROS signaling and SDF-1 release.
K. Golan, Y. Vagima, A. Ludin, T. Itkin, S. Cohen-Gur, A. Kalinkovich, O. Kollet, C. Kim, A. Schajnovitz, Y. Ovadya, et al. (2012)
Blood 119, 2478-2488
   Abstract »    Full Text »    PDF »
Amelioration of Collagen-Induced Arthritis by a Novel S1P1 Antagonist with Immunomodulatory Activities.
Y. Fujii, T. Hirayama, H. Ohtake, N. Ono, T. Inoue, T. Sakurai, T. Takayama, K. Matsumoto, N. Tsukahara, S. Hidano, et al. (2012)
J. Immunol. 188, 206-215
   Abstract »    Full Text »    PDF »
Pericyte-Derived Sphinogosine 1-Phosphate Induces the Expression of Adhesion Proteins and Modulates the Retinal Endothelial Cell Barrier.
P. G. McGuire, S. Rangasamy, J. Maestas, and A. Das (2011)
Arterioscler Thromb Vasc Biol 31, e107-e115
   Abstract »    Full Text »    PDF »
Sequential desensitization of CXCR4 and S1P5 controls natural killer cell trafficking.
K. Mayol, V. Biajoux, J. Marvel, K. Balabanian, and T. Walzer (2011)
Blood 118, 4863-4871
   Abstract »    Full Text »    PDF »
GRK2-Dependent S1PR1 Desensitization Is Required for Lymphocytes to Overcome Their Attraction to Blood.
T. I. Arnon, Y. Xu, C. Lo, T. Pham, J. An, S. Coughlin, G. W. Dorn, and J. G. Cyster (2011)
Science 333, 1898-1903
   Abstract »    Full Text »    PDF »
FTY720 (Gilenya) Phosphate Selectivity of Sphingosine 1-Phosphate Receptor Subtype 1 (S1P1) G Protein-coupled Receptor Requires Motifs in Intracellular Loop 1 and Transmembrane Domain 2.
W. J. Valentine, V. I. Godwin, D. A. Osborne, J. Liu, Y. Fujiwara, J. Van Brocklyn, R. Bittman, A. L. Parrill, and G. Tigyi (2011)
J. Biol. Chem. 286, 30513-30525
   Abstract »    Full Text »    PDF »
Characterization of a Sphingosine 1-Phosphate Receptor Antagonist Prodrug.
P. C. Kennedy, R. Zhu, T. Huang, J. L. Tomsig, T. P. Mathews, M. David, O. Peyruchaud, T. L. Macdonald, and K. R. Lynch (2011)
J. Pharmacol. Exp. Ther. 338, 879-889
   Abstract »    Full Text »    PDF »
Purification and Identification of Activating Enzymes of CS-0777, a Selective Sphingosine 1-Phosphate Receptor 1 Modulator, in Erythrocytes.
K. Yonesu, K. Kubota, M. Tamura, S.-i. Inaba, T. Honda, C. Yahara, N. Watanabe, T. Matsuoka, and F. Nara (2011)
J. Biol. Chem. 286, 24765-24775
   Abstract »    Full Text »    PDF »
Reduction of the Peripheral Blood CD56bright NK Lymphocyte Subset in FTY720-Treated Multiple Sclerosis Patients.
T. A. Johnson, B. L. Evans, B. A. Durafourt, M. Blain, Y. Lapierre, A. Bar-Or, and J. P. Antel (2011)
J. Immunol. 187, 570-579
   Abstract »    Full Text »    PDF »
Endothelium-protective sphingosine-1-phosphate provided by HDL-associated apolipoprotein M.
C. Christoffersen, H. Obinata, S. B. Kumaraswamy, S. Galvani, J. Ahnstrom, M. Sevvana, C. Egerer-Sieber, Y. A. Muller, T. Hla, L. B. Nielsen, et al. (2011)
PNAS 108, 9613-9618
   Abstract »    Full Text »    PDF »
Lipid phosphate phosphatase 3 enables efficient thymic egress.
B. Breart, W. D. Ramos-Perez, A. Mendoza, A. K. Salous, M. Gobert, Y. Huang, R. H. Adams, J. J. Lafaille, D. Escalante-Alcalde, A. J. Morris, et al. (2011)
J. Exp. Med. 208, 1267-1278
   Abstract »    Full Text »    PDF »
Sphingosine 1-Phosphate-Induced Motility and Endocytosis of Dendritic Cells Is Regulated by SWAP-70 through RhoA.
C. Ocana-Morgner, P. Reichardt, M. Chopin, S. Braungart, C. Wahren, M. Gunzer, and R. Jessberger (2011)
J. Immunol. 186, 5345-5355
   Abstract »    Full Text »    PDF »
A Phase I Clinical Trial of Safingol in Combination with Cisplatin in Advanced Solid Tumors.
M. A. Dickson, R. D. Carvajal, A. H. Merrill Jr, M. Gonen, L. M. Cane, and G. K. Schwartz (2011)
Clin. Cancer Res. 17, 2484-2492
   Abstract »    Full Text »    PDF »
Local Inactivation of Sphingosine 1-Phosphate in Lymph Nodes Induces Lymphopenia.
S.-C. Sensken, M. Nagarajan, C. Bode, and M. H. Graler (2011)
J. Immunol. 186, 3432-3440
   Abstract »    Full Text »    PDF »
Sphingosine-1-phosphate Lyase Deficiency Produces a Pro-inflammatory Response While Impairing Neutrophil Trafficking.
M. L. Allende, M. Bektas, B. G. Lee, E. Bonifacino, J. Kang, G. Tuymetova, W. Chen, J. D. Saba, and R. L. Proia (2011)
J. Biol. Chem. 286, 7348-7358
   Abstract »    Full Text »    PDF »
Sphingosine 1-phosphate (S1P): Physiology and the effects of S1P receptor modulation.
T. Hla and V. Brinkmann (2011)
Neurology 76, S3-S8
   Abstract »    Full Text »    PDF »
Impact of sphingosine 1-phosphate modulation on immune outcomes.
D. D. Pinschewer, V. Brinkmann, and D. Merkler (2011)
Neurology 76, S15-S19
   Abstract »    Full Text »    PDF »
Low body temperature governs the decline of circulating lymphocytes during hibernation through sphingosine-1-phosphate.
H. R. Bouma, F. G. M. Kroese, J. W. Kok, F. Talaei, A. S. Boerema, A. Herwig, O. Draghiciu, A. van Buiten, A. H. Epema, A. van Dam, et al. (2011)
PNAS 108, 2052-2057
   Abstract »    Full Text »    PDF »
FTY720 (fingolimod) efficacy in an animal model of multiple sclerosis requires astrocyte sphingosine 1-phosphate receptor 1 (S1P1) modulation.
J. W. Choi, S. E. Gardell, D. R. Herr, R. Rivera, C.-W. Lee, K. Noguchi, S. T. Teo, Y. C. Yung, M. Lu, G. Kennedy, et al. (2011)
PNAS 108, 751-756
   Abstract »    Full Text »    PDF »
Sphingosine-1-Phosphate Receptor-2 Function in Myeloid Cells Regulates Vascular Inflammation and Atherosclerosis.
A. Skoura, J. Michaud, D.-S. Im, S. Thangada, Y. Xiong, J. D. Smith, and T. Hla (2011)
Arterioscler Thromb Vasc Biol 31, 81-85
   Abstract »    Full Text »    PDF »
Shaping of terminal megakaryocyte differentiation and proplatelet development by sphingosine-1-phosphate receptor S1P4.
S. Golfier, S. Kondo, T. Schulze, T. Takeuchi, G. Vassileva, A. H. Achtman, M. H. Graler, S. J. Abbondanzo, M. Wiekowski, E. Kremmer, et al. (2010)
FASEB J 24, 4701-4710
   Abstract »    Full Text »    PDF »
The Sphingosine 1-Phosphate Receptor, S1PR1, Plays a Prominent But Not Exclusive Role in Enhancing the Excitability of Sensory Neurons.
X. X. Chi and G. D. Nicol (2010)
J Neurophysiol 104, 2741-2748
   Abstract »    Full Text »    PDF »
Blood sphingolipidomics in healthy humans: impact of sample collection methodology.
S. M. Hammad, J. S. Pierce, F. Soodavar, K. J. Smith, M. M. Al Gadban, B. Rembiesa, R. L. Klein, Y. A. Hannun, J. Bielawski, and A. Bielawska (2010)
J. Lipid Res. 51, 3074-3087
   Abstract »    Full Text »    PDF »
Role of alkaline ceramidases in the generation of sphingosine and its phosphate in erythrocytes.
R. Xu, W. Sun, J. Jin, L. M. Obeid, and C. Mao (2010)
FASEB J 24, 2507-2515
   Abstract »    Full Text »    PDF »
Neural Crest-Derived Pericytes Promote Egress of Mature Thymocytes at the Corticomedullary Junction.
M. A. Zachariah and J. G. Cyster (2010)
Science 328, 1129-1135
   Abstract »    Full Text »    PDF »
S1P1 receptor directs the release of immature B cells from bone marrow into blood.
M. L. Allende, G. Tuymetova, B. G. Lee, E. Bonifacino, Y.-P. Wu, and R. L. Proia (2010)
J. Exp. Med. 207, 1113-1124
   Abstract »    Full Text »    PDF »
Cleavage of sphingosine kinase 2 by caspase-1 provokes its release from apoptotic cells.
A. Weigert, S. Cremer, M. V. Schmidt, A. von Knethen, C. Angioni, G. Geisslinger, and B. Brune (2010)
Blood 115, 3531-3540
   Abstract »    Full Text »    PDF »
Redistribution of Sphingosine 1-Phosphate by Sphingosine Kinase 2 Contributes to Lymphopenia.
S. C. Sensken, C. Bode, M. Nagarajan, U. Peest, O. Pabst, and M. H. Graler (2010)
J. Immunol. 184, 4133-4142
   Abstract »    Full Text »    PDF »
Down-regulation of S1P1 Receptor Surface Expression by Protein Kinase C Inhibition.
S.-C. Sensken and M. H. Graler (2010)
J. Biol. Chem. 285, 6298-6307
   Abstract »    Full Text »    PDF »
Lymphatic endothelial cell sphingosine kinase activity is required for lymphocyte egress and lymphatic patterning.
T. H.M. Pham, P. Baluk, Y. Xu, I. Grigorova, A. J. Bankovich, R. Pappu, S. R. Coughlin, D. M. McDonald, S. R. Schwab, and J. G. Cyster (2010)
J. Exp. Med. 207, 17-27
   Abstract »    Full Text »    PDF »
T-bet-dependent S1P5 expression in NK cells promotes egress from lymph nodes and bone marrow.
C. N. Jenne, A. Enders, R. Rivera, S. R. Watson, A. J. Bankovich, J. P. Pereira, Y. Xu, C. M. Roots, J. N. Beilke, A. Banerjee, et al. (2009)
J. Exp. Med. 206, 2469-2481
   Abstract »    Full Text »    PDF »
Discontinued Postnatal Thymocyte Development in Sphingosine 1-Phosphate-Lyase-Deficient Mice.
C. Weber, A. Krueger, A. Munk, C. Bode, P. P. Van Veldhoven, and M. H. Graler (2009)
J. Immunol. 183, 4292-4301
   Abstract »    Full Text »    PDF »
Bone Marrow Progenitor Cells Induce Endothelial Adherens Junction Integrity by Sphingosine-1-Phosphate-Mediated Rac1 and Cdc42 Signaling.
Y. D. Zhao, H. Ohkawara, J. Rehman, K. K. Wary, S. M. Vogel, R. D. Minshall, Y.-Y. Zhao, and A. B. Malik (2009)
Circ. Res. 105, 696-704
   Abstract »    Full Text »    PDF »
Characterization of the ATP-dependent Sphingosine 1-Phosphate Transporter in Rat Erythrocytes.
N. Kobayashi, N. Kobayashi, A. Yamaguchi, and T. Nishi (2009)
J. Biol. Chem. 284, 21192-21200
   Abstract »    Full Text »    PDF »
Distinct Roles of Sphingosine Kinase 1 and 2 in Murine Collagen-Induced Arthritis.
W.-Q. Lai, A. W. Irwan, H. H. Goh, A. J. Melendez, I. B. McInnes, and B. P. Leung (2009)
J. Immunol. 183, 2097-2103
   Abstract »    Full Text »    PDF »
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 »
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 »
Sphingosine-1-phosphate and modulation of vascular tone.
J. Igarashi and T. Michel (2009)
Cardiovasc Res 82, 212-220
   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 »
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 »
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)
Annals of Clinical Biochemistry 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 »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882