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.

Science 9 September 2005:
Vol. 309. no. 5741, pp. 1735 - 1739
DOI: 10.1126/science.1113640
Prev | Table of Contents | Next

Reports

Lymphocyte Sequestration Through S1P Lyase Inhibition and Disruption of S1P Gradients

Susan R. Schwab,1 João P. Pereira,1 Mehrdad Matloubian,1 Ying Xu,1 Yong Huang,2 Jason G. Cyster1*

Lymphocyte egress from the thymus and from peripheral lymphoid organs depends on sphingosine 1-phosphate (S1P) receptor-1 and is thought to occur in response to circulatory S1P. However, the existence of an S1P gradient between lymphoid organs and blood or lymph has not been established. To further define egress requirements, we addressed why treatment with the food colorant 2-acetyl-4-tetrahydroxybutylimidazole (THI) induces lymphopenia. We found that S1P abundance in lymphoid tissues of mice is normally low but increases more than 100-fold after THI treatment and that this treatment inhibits the S1P-degrading enzyme S1P lyase. We conclude that lymphocyte egress is mediated by S1P gradients that are established by S1P lyase activity and that the lyase may represent a novel immunosuppressant drug target.

1 Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143–0414, USA.
2 Drug Studies Unit, Department of Biopharmaceutical Sciences, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143–0414, USA.

* To whom correspondence should be addressed. E-mail: cyster{at}itsa.ucsf.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
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 »
Involvement of Sphingosine 1-Phosphate (SIP)/S1P3 Signaling in Cholestasis-Induced Liver Fibrosis.
C. Li, X. Jiang, L. Yang, X. Liu, S. Yue, and L. Li (2009)
Am. J. Pathol. 175, 1464-1472
   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 »
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 »
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 »
Role of the Molybdoflavoenzyme Aldehyde Oxidase Homolog 2 in the Biosynthesis of Retinoic Acid: Generation and Characterization of a Knockout Mouse.
M. Terao, M. Kurosaki, M. M. Barzago, M. Fratelli, R. Bagnati, A. Bastone, C. Giudice, E. Scanziani, A. Mancuso, C. Tiveron, et al. (2009)
Mol. Cell. Biol. 29, 357-377
   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 »
Tre1 GPCR initiates germ cell transepithelial migration by regulating Drosophila melanogaster E-cadherin.
P. S. Kunwar, H. Sano, A. D. Renault, V. Barbosa, N. Fuse, and R. Lehmann (2008)
J. Cell Biol. 183, 157-168
   Abstract »    Full Text »    PDF »
Local Not Systemic Modulation of Dendritic Cell S1P Receptors in Lung Blunts Virus-Specific Immune Responses to Influenza.
D. Marsolais, B. Hahm, K. H. Edelmann, K. B. Walsh, M. Guerrero, Y. Hatta, Y. Kawaoka, E. Roberts, M. B. A. Oldstone, and H. Rosen (2008)
Mol. Pharmacol. 74, 896-903
   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 »
Identifying Key Residues of Sphinganine-1-phosphate Lyase for Function in Vivo and in Vitro.
D. Mukhopadhyay, K. S. Howell, H. Riezman, and G. Capitani (2008)
J. Biol. Chem. 283, 20159-20169
   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-dependent trafficking of peritoneal B cells requires functional NF{kappa}B-inducing kinase in stromal cells.
J. Kunisawa, M. Gohda, Y. Kurashima, I. Ishikawa, M. Higuchi, and H. Kiyono (2008)
Blood 111, 4646-4652
   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 »
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 »
A rapid fluorescence assay for sphingosine-1-phosphate lyase enzyme activity.
P. Bandhuvula, H. Fyrst, and J. D. Saba (2007)
J. Lipid Res. 48, 2769-2778
   Abstract »    Full Text »    PDF »
Sphingosine 1-phosphate dependence in the regulation of lymphocyte trafficking to the gut epithelium.
J. Kunisawa, Y. Kurashima, M. Higuchi, M. Gohda, I. Ishikawa, I. Ogahara, N. Kim, M. Shimizu, and H. Kiyono (2007)
J. Exp. Med. 204, 2335-2348
   Abstract »    Full Text »    PDF »
A sphingosine kinase 1 mutation sensitizes the myocardium to ischemia/reperfusion injury.
Z.-Q. Jin, J. Zhang, Y. Huang, H. E. Hoover, D. A. Vessey, and J. S. Karliner (2007)
Cardiovasc Res 76, 41-50
   Abstract »    Full Text »    PDF »
Promotion of Lymphocyte Egress into Blood and Lymph by Distinct Sources of Sphingosine-1-Phosphate.
R. Pappu, S. R. Schwab, I. Cornelissen, J. P. Pereira, J. B. Regard, Y. Xu, E. Camerer, Y.-W. Zheng, Y. Huang, J. G. Cyster, et al. (2007)
Science 316, 295-298
   Abstract »    Full Text »    PDF »
Erythrocytes store and release sphingosine 1-phosphate in blood.
P. Hanel, P. Andreani, and M. H. Graler (2007)
FASEB J 21, 1202-1209
   Abstract »    Full Text »    PDF »
A central role for DOCK2 during interstitial lymphocyte motility and sphingosine-1-phosphate-mediated egress.
C. Nombela-Arrieta, T. R. Mempel, S. F. Soriano, I. Mazo, M. P. Wymann, E. Hirsch, C. Martinez-A., Y. Fukui, U. H. von Andrian, and J. V. Stein (2007)
J. Exp. Med. 204, 497-510
   Abstract »    Full Text »    PDF »
CC Chemokine Receptor 7 Contributes to Gi-Dependent T Cell Motility in the Lymph Node.
T. Okada and J. G. Cyster (2007)
J. Immunol. 178, 2973-2978
   Abstract »    Full Text »    PDF »
The immunosuppressant drug FTY720 inhibits cytosolic phospholipase A2 independently of sphingosine-1-phosphate receptors.
S. G. Payne, C. A. Oskeritzian, R. Griffiths, P. Subramanian, S. E. Barbour, C. E. Chalfant, S. Milstien, and S. Spiegel (2007)
Blood 109, 1077-1085
   Abstract »    Full Text »    PDF »
Distinctive T Cell-suppressive Signals from Nuclearized Type 1 Sphingosine 1-Phosphate G Protein-coupled Receptors.
J.-J. Liao, M.-C. Huang, M. Graler, Y. Huang, H. Qiu, and E. J. Goetzl (2007)
J. Biol. Chem. 282, 1964-1972
   Abstract »    Full Text »    PDF »
Sphingosine-1-Phosphate Modulates Both Lipolysis and Leptin Production in Differentiated Rat White Adipocytes.
D.-J. Jun, J.-H. Lee, B.-H. Choi, T.-K. Koh, D.-C. Ha, M.-W. Jeong, and K.-T. Kim (2006)
Endocrinology 147, 5835-5844
   Abstract »    Full Text »    PDF »
Plasma cell S1P1 expression determines secondary lymphoid organ retention versus bone marrow tropism.
K. Kabashima, N. M. Haynes, Y. Xu, S. L. Nutt, M. L. Allende, R. L. Proia, and J. G. Cyster (2006)
J. Exp. Med. 203, 2683-2690
   Abstract »    Full Text »    PDF »
Type I interferons directly regulate lymphocyte recirculation and cause transient blood lymphopenia.
E. Kamphuis, T. Junt, Z. Waibler, R. Forster, and U. Kalinke (2006)
Blood 108, 3253-3261
   Abstract »    Full Text »    PDF »
Sphingosine-1-phosphate lyase potentiates apoptosis via p53- and p38-dependent pathways and is down-regulated in colon cancer.
B. Oskouian, P. Sooriyakumaran, A. D. Borowsky, A. Crans, L. Dillard-Telm, Y. Y. Tam, P. Bandhuvula, and J. D. Saba (2006)
PNAS 103, 17384-17389
   Abstract »    Full Text »    PDF »
Intracellular role for sphingosine kinase 1 in intestinal adenoma cell proliferation..
M. Kohno, M. Momoi, M. L. Oo, J.-H. Paik, Y.-M. Lee, K. Venkataraman, Y. Ai, A. P. Ristimaki, H. Fyrst, H. Sano, et al. (2006)
Mol. Cell. Biol. 26, 7211-7223
   Abstract »    Full Text »    PDF »
Sphingosine 1-Phosphate Affects Cytokine-Induced Apoptosis in Rat Pancreatic Islet {beta}-Cells.
S. G. Laychock, S. M. Sessanna, M.-H. Lin, and L. D. Mastrandrea (2006)
Endocrinology 147, 4705-4712
   Abstract »    Full Text »    PDF »
The value of animal models for drug development in multiple sclerosis.
M. A. Friese, X. Montalban, N. Willcox, J. I. Bell, R. Martin, and L. Fugger (2006)
Brain 129, 1940-1952
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

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