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The influence of sphingosine-1-phosphate receptor signaling on lymphocyte trafficking: How a bioactive lipid mediator grew up from an “immature” vascular maturation factor to a “mature” mediator of lymphocyte behavior and function

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Abstract

Since the initial observations that highlighted the importance of lymphocyte trafficking for immune responses, the pathways utilized by B and T lymphocytes to recirculate and properly position themselves have been intensely studied. Most of the chemoattractants along with their cognate receptors that affect lymphocyte trafficking have been identified. Some of their functions are promotion of lymphocyte ingress into immune organs, localization of cells to specific regions within those organs, maintenance of lymphocyte basal motility in immune organs, facilitation of lymphocyte egress from these organs, and control of migration and homing of lymphocytes in the periphery. Since the seminal discovery that agonism of sphingosine-1-phosphate receptors evokes changes in lymphocyte homing and trafficking, considerable effort has been undertaken to characterize the mechanism utilized by these receptors to influence lymphocyte behavior. This review will focus on the influence of sphingosine-1-phosphate signaling system on lymphocyte localization, egress from lymph organs, and its effects on the lymphatic vasculature.

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References

  1. Liu Y, et al. Edg-1, the G protein-coupled receptor for sphingosine-1-phosphate, is essential for vascular maturation. J Clin Invest. 2000;106:951–61.

    PubMed  CAS  Google Scholar 

  2. Nava VE, Hobson JP, Murthy S, Milstien S, Spiegel S. Sphingosine kinase type 1 promotes estrogen-dependent tumorigenesis of breast cancer MCF-7 cells. Exp Cell Res. 2002;281:115–27.

    PubMed  CAS  Google Scholar 

  3. Liu H, et al. Molecular cloning and functional characterization of a novel mammalian sphingosine kinase type 2 isoform. J Biol Chem. 2000;275:19513–20.

    PubMed  CAS  Google Scholar 

  4. Yang L, Yatomi Y, Miura Y, Satoh K, Ozaki Y. Metabolism and functional effects of sphingolipids in blood cells. Br J Haematol. 1999;107:282–93.

    PubMed  CAS  Google Scholar 

  5. Hanel P, Andreani P, Graler MH. Erythrocytes store and release sphingosine 1-phosphate in blood. Faseb J. 2007;21:1202–9.

    PubMed  Google Scholar 

  6. Ito K, et al. Lack of sphingosine 1-phosphate-degrading enzymes in erythrocytes. Biochem Biophys Res Commun. 2007;357:212–7.

    PubMed  CAS  Google Scholar 

  7. Kihara A, Igarashi Y. Production and release of sphingosine 1-phosphate and the phosphorylated form of the immunomodulator FTY720. Biochim Biophys Acta. 2008;1781(9):496–502.

    PubMed  CAS  Google Scholar 

  8. Pappu R, et al. Promotion of lymphocyte egress into blood and lymph by distinct sources of sphingosine-1-phosphate. Science. 2007;316:295–8.

    PubMed  CAS  Google Scholar 

  9. Pilquil C, et al. Co-ordinate regulation of growth factor receptors and lipid phosphate phosphatase-1 controls cell activation by exogenous lysophosphatidate. Biochem Soc Trans. 2001;29:825–30.

    PubMed  CAS  Google Scholar 

  10. Le Stunff H, et al. Role of sphingosine-1-phosphate phosphatase 1 in epidermal growth factor-induced chemotaxis. J Biol Chem. 2004;279:34290–7.

    PubMed  Google Scholar 

  11. Ogawa C, Kihara A, Gokoh M, Igarashi Y. Identification and characterization of a novel human sphingosine-1-phosphate phosphohydrolase, hSPP2. J Biol Chem. 2003;278:1268–72.

    PubMed  CAS  Google Scholar 

  12. Le Stunff H, Galve-Roperh I, Peterson C, Milstien S, Spiegel S. Sphingosine-1-phosphate phosphohydrolase in regulation of sphingolipid metabolism and apoptosis. J Cell Biol. 2002;158:1039–49.

    PubMed  Google Scholar 

  13. Zhou J, Saba JD. Identification of the first mammalian sphingosine phosphate lyase gene and its functional expression in yeast. Biochem Biophys Res Commun. 1998;242:502–7.

    PubMed  CAS  Google Scholar 

  14. Saba JD, Nara F, Bielawska A, Garrett S, Hannun YA. The BST1 gene of Saccharomyces cerevisiae is the sphingosine-1-phosphate lyase. J Biol Chem. 1997;272:26087–90.

    PubMed  CAS  Google Scholar 

  15. Goodemote KA, Mattie ME, Berger A, Spiegel S. Involvement of a pertussis toxin-sensitive G protein in the mitogenic signaling pathways of sphingosine 1-phosphate. J Biol Chem. 1995;270:10272–7.

    PubMed  CAS  Google Scholar 

  16. Wu J, Spiegel S, Sturgill TW. Sphingosine 1-phosphate rapidly activates the mitogen-activated protein kinase pathway by a G protein-dependent mechanism. J Biol Chem. 1995;270:11484–8.

    PubMed  CAS  Google Scholar 

  17. Hla T, Maciag T. An abundant transcript induced in differentiating human endothelial cells encodes a polypeptide with structural similarities to G-protein-coupled receptors. J Biol Chem. 1990;265:9308–13.

    PubMed  CAS  Google Scholar 

  18. An S, Goetzl EJ, Lee H. Signaling mechanisms and molecular characteristics of G protein-coupled receptors for lysophosphatidic acid and sphingosine 1-phosphate. J Cell Biochem Suppl. 1998;30–31:147–57.

    PubMed  Google Scholar 

  19. Zondag GC, Postma FR, Etten IV, Verlaan I, Moolenaar WH. Sphingosine 1-phosphate signalling through the G-protein-coupled receptor Edg-1. Biochem J. 1998;330(Pt 2):605–9.

    PubMed  CAS  Google Scholar 

  20. Cuvillier O, et al. Suppression of ceramide-mediated programmed cell death by sphingosine-1-phosphate. Nature. 1996;381:800–3.

    PubMed  CAS  Google Scholar 

  21. Hobson JP, et al. Role of the sphingosine-1-phosphate receptor EDG-1 in PDGF-induced cell motility. Science. 2001;291:1800–3.

    PubMed  CAS  Google Scholar 

  22. Paik JH, Chae S, Lee MJ, Thangada S, Hla T. Sphingosine 1-phosphate-induced endothelial cell migration requires the expression of EDG-1 and EDG-3 receptors and Rho-dependent activation of alpha vbeta3- and beta1-containing integrins. J Biol Chem. 2001;276:11830–7.

    PubMed  CAS  Google Scholar 

  23. Zhang H, et al. Sphingosine-1-phosphate, a novel lipid, involved in cellular proliferation. J Cell Biol. 1991;114:155–67.

    PubMed  CAS  Google Scholar 

  24. Mandala S, et al. Alteration of lymphocyte trafficking by sphingosine-1-phosphate receptor agonists. Science. 2002;296:346–9.

    PubMed  CAS  Google Scholar 

  25. Xie JH, et al. Sphingosine-1-phosphate receptor agonism impairs the efficiency of the local immune response by altering trafficking of naive and antigen-activated CD4+ T cells. J Immunol. 2003;170:3662–70.

    PubMed  CAS  Google Scholar 

  26. Allende ML, et al. Mice deficient in sphingosine kinase 1 are rendered lymphopenic by FTY720. J Biol Chem. 2004;279:52487–92.

    PubMed  CAS  Google Scholar 

  27. Matloubian M, et al. Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1. Nature. 2004;427:355–60.

    PubMed  CAS  Google Scholar 

  28. Sanna MG, et al. Sphingosine 1-phosphate (S1P) receptor subtypes S1P1 and S1P3, respectively, regulate lymphocyte recirculation and heart rate. J Biol Chem. 2004;279:13839–48.

    PubMed  CAS  Google Scholar 

  29. Halin C, et al. The S1P-analog FTY720 differentially modulates T-cell homing via HEV: T-cell-expressed S1P1 amplifies integrin activation in peripheral lymph nodes but not in Peyer patches. Blood. 2005;106:1314–22.

    PubMed  CAS  Google Scholar 

  30. Kharel Y, et al. Sphingosine kinase 2 is required for modulation of lymphocyte traffic by FTY720. J Biol Chem. 2005;280:36865–72.

    PubMed  CAS  Google Scholar 

  31. Morris MA, et al. Transient T cell accumulation in lymph nodes and sustained lymphopenia in mice treated with FTY720. Eur J Immunol. 2005;35:3570–80.

    PubMed  CAS  Google Scholar 

  32. Kunisawa J, et al. Sphingosine 1-phosphate dependence in the regulation of lymphocyte trafficking to the gut epithelium. J Exp Med. 2007;204:2335–48.

    PubMed  CAS  Google Scholar 

  33. Balatoni B, et al. FTY720 sustains and restores neuronal function in the DA rat model of MOG-induced experimental autoimmune encephalomyelitis. Brain Res Bull. 2007;74:307–16.

    PubMed  CAS  Google Scholar 

  34. Foster CA, et al. FTY720 rescue therapy in the dark agouti rat model of experimental autoimmune encephalomyelitis: expression of central nervous system genes and reversal of blood–brain–barrier damage. Brain Pathol. 2008; in press.

  35. Brinkmann V, Cyster JG, Hla T. FTY720: sphingosine 1-phosphate receptor–1 in the control of lymphocyte egress and endothelial barrier function. Am J Transplant. 2004;4:1019–25.

    PubMed  CAS  Google Scholar 

  36. Forrest M, et al. Immune cell regulation and cardiovascular effects of sphingosine 1-phosphate receptor agonists in rodents are mediated via distinct receptor subtypes. J Pharmacol Exp Ther. 2004;309:758–68.

    PubMed  CAS  Google Scholar 

  37. Zhang J, et al. Signals from type 1 sphingosine 1-phosphate receptors enhance adult mouse cardiac myocyte survival during hypoxia. Am J Physiol Heart Circ Physiol. 2007;293:H3150–8.

    PubMed  CAS  Google Scholar 

  38. Xin C, et al. Sphingosine 1-phosphate cross-activates the Smad signaling cascade and mimics transforming growth factor-beta-induced cell responses. J Biol Chem. 2004;279:35255–62.

    PubMed  CAS  Google Scholar 

  39. Whetzel AM, et al. Sphingosine-1 phosphate prevents monocyte/endothelial interactions in type 1 diabetic NOD mice through activation of the S1P1 receptor. Circ Res. 2006;99:731–9.

    PubMed  CAS  Google Scholar 

  40. Bolick DT, et al. Sphingosine-1-phosphate prevents tumor necrosis factor-{alpha}-mediated monocyte adhesion to aortic endothelium in mice. Arterioscler Thromb Vasc Biol. 2005;25:976–81.

    PubMed  CAS  Google Scholar 

  41. Fujita T, et al. Fungal metabolites. Part 11. A potent immunosuppressive activity found in Isaria sinclairii metabolite. J Antibiot (Tokyo). 1994;47:208–15.

    CAS  Google Scholar 

  42. Brinkmann V, Pinschewer DD, Feng L, Chen S. FTY720: altered lymphocyte traffic results in allograft protection. Transplantation. 2001;72:764–9.

    PubMed  CAS  Google Scholar 

  43. Brinkmann V, et al. FTY720 alters lymphocyte homing and protects allografts without inducing general immunosuppression. Transplant Proc. 2001;33:530–1.

    PubMed  CAS  Google Scholar 

  44. Zhang Z, Zhang ZY, Fauser U, Schluesener HJ. FTY720 ameliorates experimental autoimmune neuritis by inhibition of lymphocyte and monocyte infiltration into peripheral nerves. Exp Neurol. 2008;210:681–90.

    PubMed  CAS  Google Scholar 

  45. Foster CA, et al. Brain penetration of the oral immunomodulatory drug FTY720 and its phosphorylation in the central nervous system during experimental autoimmune encephalomyelitis: consequences for mode of action in multiple sclerosis. J Pharmacol Exp Ther. 2007;323:469–75.

    PubMed  CAS  Google Scholar 

  46. Kohno T, et al. A novel immunomodulator, FTY720, prevents development of experimental autoimmune myasthenia gravis in C57BL/6 mice. Biol Pharm Bull. 2005;28:736–9.

    PubMed  CAS  Google Scholar 

  47. Pinschewer DD, et al. FTY720 immunosuppression impairs effector T cell peripheral homing without affecting induction, expansion, and memory. J Immunol. 2000;164:5761–70.

    PubMed  CAS  Google Scholar 

  48. Liu Q, et al. FTY720 demonstrates promising preclinical activity for chronic lymphocytic leukemia and lymphoblastic leukemia/lymphoma. Blood. 2008;111:275–84.

    PubMed  CAS  Google Scholar 

  49. Kaudel CP, et al. FTY720 for treatment of ischemia-reperfusion injury following complete renal ischemia; impact on long-term survival and T-lymphocyte tissue infiltration. Transplant Proc. 2007;39:499–502.

    PubMed  CAS  Google Scholar 

  50. Kaudel CP, et al. FTY720 application following isolated warm liver ischemia improves long-term survival and organ protection in a mouse model. Transplant Proc. 2007;39:493–8.

    PubMed  CAS  Google Scholar 

  51. Schmid G, et al. The immunosuppressant FTY720 inhibits tumor angiogenesis via the sphingosine 1-phosphate receptor 1. J Cell Biochem. 2007;101:259–70.

    PubMed  CAS  Google Scholar 

  52. Silva FR, Silva LB, Cury PM, Burdmann EA, Bueno V. FTY720 in combination with cyclosporine—an analysis of skin allograft survival and renal function. Int Immunopharmacol. 2006;6:1911–8.

    PubMed  CAS  Google Scholar 

  53. Pan S, et al. A monoselective sphingosine–1-phosphate receptor-1 agonist prevents allograft rejection in a stringent rat heart transplantation model. Chem Biol. 2006;13:1227–34.

    PubMed  CAS  Google Scholar 

  54. Deguchi Y, et al. The S1P receptor modulator FTY720 prevents the development of experimental colitis in mice. Oncol Rep. 2006;16:699–703.

    PubMed  CAS  Google Scholar 

  55. Meno-Tetang GM, et al. Physiologically based pharmacokinetic modeling of FTY720 (2-amino-2[2-(-4-octylphenyl)ethyl]propane-1, 3-diol hydrochloride) in rats after oral and intravenous doses. Drug Metab Dispos. 2006;34:1480–7.

    PubMed  CAS  Google Scholar 

  56. Man K, et al. Fat-derived hormone adiponectin combined with FTY720 significantly improves small-for-size fatty liver graft survival. Am J Transplant. 2006;6:467–76.

    PubMed  CAS  Google Scholar 

  57. Troncoso P, Ortiz AM, Dominguez J, Kahan BD. Use of FTY 720 and ICAM-1 antisense oligonucleotides for attenuating chronic renal damage secondary to ischemia-reperfusion injury. Transplant Proc. 2005;37:4284–8.

    PubMed  CAS  Google Scholar 

  58. Penuelas-Rivas G, et al. FTY720 inhibits TH1-mediated allogeneic humoral immune response. Transplant Proc. 2005;37:4124–6.

    PubMed  CAS  Google Scholar 

  59. Kim JY, et al. Effect of FTY720 on chronic cyclosporine nephropathy in rats. Transplantation. 2005;80:1323–30.

    PubMed  CAS  Google Scholar 

  60. Ueda H, et al. Preoperative administration of FTY720 prolonged renal allograft survival. Transpl Immunol. 2005;14:1–8.

    PubMed  CAS  Google Scholar 

  61. Yan S, et al. Control of intestinal allograft rejection by FTY720 and costimulation blockade. Transplant Proc. 2005;37:114–5.

    PubMed  CAS  Google Scholar 

  62. Sedlakova K, Muckersie E, Robertson M, Filipec M, Forrester JV. FTY720 in corneal concordant xenotransplantation. Transplantation. 2005;79:297–303.

    PubMed  CAS  Google Scholar 

  63. Sakagawa T, Kiyochi H, Honda K, Kobayashi N. Rejection following donor or recipient preoperative treatment with FTY720 in rat small bowel transplantation. Transpl Immunol. 2004;13:161–8.

    PubMed  CAS  Google Scholar 

  64. Mayer K, et al. FTY720 prolongs clear corneal allograft survival with a differential effect on different lymphocyte populations. Br J Ophthalmol. 2004;88:915–9.

    PubMed  CAS  Google Scholar 

  65. Wijkstrom M, et al. Islet allograft survival in nonhuman primates immunosuppressed with basiliximab, RAD, and FTY720. Transplantation. 2004;77:827–35.

    PubMed  CAS  Google Scholar 

  66. Budde K, et al. FTY720 (fingolimod) in renal transplantation. Clin Transplant. 2006;20(Suppl 17):17–24.

    PubMed  Google Scholar 

  67. Kaudel CP, et al. FTY720 for treatment of ischemia-reperfusion injury following complete renal ischemia in C57/BL6 mice. Transplant Proc. 2006;38:679–81.

    PubMed  CAS  Google Scholar 

  68. Vaessen LM, van Besouw NM, Mol WM, Ijzermans JN, Weimar W. FTY720 treatment of kidney transplant patients: a differential effect on B cells, naive T cells, memory T cells and NK cells. Transpl Immunol. 2006;15:281–8.

    PubMed  CAS  Google Scholar 

  69. Skerjanec A, et al. FTY720, a novel immunomodulator in de novo kidney transplant patients: pharmacokinetics and exposure-response relationship. J Clin Pharmacol. 2005;45:1268–78.

    PubMed  CAS  Google Scholar 

  70. Suleiman M, Cury PM, Pestana JO, Burdmann EA, Bueno V. FTY720 prevents renal T-cell infiltration after ischemia/reperfusion injury. Transplant Proc. 2005;37:373–4.

    PubMed  CAS  Google Scholar 

  71. Galvao VR, Ginoza M, Franco M, Burdmann EA, Bueno V. Prolonged administration of FTY720 does not cause renal toxicity in mice. Transplant Proc. 2005;37:112–3.

    PubMed  CAS  Google Scholar 

  72. Chiba K, et al. Immunosuppressive activity of FTY720, sphingosine 1-phosphate receptor agonist: I. Prevention of allograft rejection in rats and dogs by FTY720 and FTY720-phosphate. Transplant Proc. 2005;37:102–6.

    PubMed  CAS  Google Scholar 

  73. Shi Y, et al. A novel immunosuppressant FTY720 ameliorates proteinuria and alterations of intrarenal adrenomedullin in rats with autoimmune glomerulonephritis. Regul Pept. 2005;127:233–8.

    PubMed  CAS  Google Scholar 

  74. Suzuki T, et al. A new immunosuppressant, FTY720, in canine kidney transplantation: effect of single-drug, induction and combination treatments. Transpl Int. 2004;17:574–84.

    PubMed  CAS  Google Scholar 

  75. Wang M, et al. Protective effects of FTY720 on chronic allograft nephropathy by reducing late lymphocytic infiltration. Kidney Int. 2004;66:1248–56.

    PubMed  CAS  Google Scholar 

  76. Bohler T, et al. FTY720 mediates apoptosis-independent lymphopenia in human renal allograft recipients: different effects on CD62L+ and CCR5+ T lymphocytes. Transplantation. 2004;77:1424–32.

    PubMed  Google Scholar 

  77. Dragun D, et al. FTY720-induced lymphocyte homing modulates post-transplant preservation/reperfusion injury. Kidney Int. 2004;65:1076–83.

    PubMed  CAS  Google Scholar 

  78. Kahan BD, et al. Pharmacodynamics, pharmacokinetics, and safety of multiple doses of FTY720 in stable renal transplant patients: a multicenter, randomized, placebo-controlled, phase I study. Transplantation. 2003;76:1079–84.

    PubMed  CAS  Google Scholar 

  79. Zhang L, et al. Pretreatment with FTY720 alone induced long-term survival of mouse heart allograft. Transplant Proc. 2003;35:567–8.

    PubMed  CAS  Google Scholar 

  80. Schuurman HJ, et al. Oral efficacy of the new immunomodulator FTY720 in cynomolgus monkey kidney allotransplantation, given alone or in combination with cyclosporine or RAD. Transplantation. 2002;74:951–60.

    PubMed  CAS  Google Scholar 

  81. Boehler T, Schuetz M, Budde K, Neumayer H, Waiser J. FTY720 alters the composition of T-lymphocyte subpopulations in the peripheral blood compartment of renal transplant patients. Transplant Proc. 2002;34:2242–3.

    PubMed  CAS  Google Scholar 

  82. Brinkmann V, et al. The immune modulator FTY720 targets sphingosine 1-phosphate receptors. J Biol Chem. 2002;277:21453–7.

    PubMed  CAS  Google Scholar 

  83. Budde K, et al. First human trial of FTY720, a novel immunomodulator, in stable renal transplant patients. J Am Soc Nephrol. 2002;13:1073–83.

    PubMed  CAS  Google Scholar 

  84. Kahan BD. Update on pharmacokinetic/pharmacodynamic studies with FTY720 and sirolimus. Ther Drug Monit. 2002;24:47–52.

    PubMed  CAS  Google Scholar 

  85. Quesniaux V, Menninger K, Audet M, Gaschen L, Schuurman HJ. FTY-720 is efficacious in monkey kidney transplantation. Transplant Proc. 2001;33:2374–5.

    PubMed  CAS  Google Scholar 

  86. Troncoso P, Ortiz M, Martinez L, Kahan BD. FTY 720 prevents ischemic reperfusion damage in rat kidneys. Transplant Proc. 2001;33:857–9.

    PubMed  CAS  Google Scholar 

  87. Bohler T, et al. FTY 720A mediates reduction of lymphocyte counts in human renal allograft recipients by an apoptosis-independent mechanism. Transpl Int. 2000;13(Suppl 1):S311–3.

    PubMed  Google Scholar 

  88. Omura T, et al. A short-course therapy with FTY720 prolongs allograft survival after canine kidney transplantation. Transplant Proc. 1999;31:2783–4.

    PubMed  CAS  Google Scholar 

  89. Troncoso P, et al. Prophylaxis of acute renal allograft rejection using FTY720 in combination with subtherapeutic doses of cyclosporine. Transplantation. 1999;67:145–51.

    PubMed  CAS  Google Scholar 

  90. Yuzawa K, et al. An effect of FTY720 on acute rejection in canine renal transplantation. Transplant Proc. 1998;30:1046.

    PubMed  CAS  Google Scholar 

  91. Suzuki S, et al. An immunosuppressive regimen using FTY720 combined with cyclosporin in canine kidney transplantation. Transpl Int. 1998;11:95–101.

    PubMed  CAS  Google Scholar 

  92. Suzuki S, et al. A novel immunosuppressant, FTY720, with a unique mechanism of action, induces long-term graft acceptance in rat and dog allotransplantation. Transplantation. 1996;61:200–5.

    PubMed  CAS  Google Scholar 

  93. Brinkmann V, Pinschewer D, Chiba K, Feng L. FTY720: a novel transplantation drug that modulates lymphocyte traffic rather than activation. Trends Pharmacol Sci. 2000;21:49–52.

    PubMed  CAS  Google Scholar 

  94. Henning G, et al. CC chemokine receptor 7-dependent and -independent pathways for lymphocyte homing: modulation by FTY720. J Exp Med. 2001;194:1875–81.

    PubMed  CAS  Google Scholar 

  95. Zemann B, et al. Sphingosine kinase type 2 is essential for lymphopenia induced by the immunomodulatory drug FTY720. Blood. 2006;107:1454–8.

    PubMed  CAS  Google Scholar 

  96. Paugh SW, Payne SG, Barbour SE, Milstien S, Spiegel S. The immunosuppressant FTY720 is phosphorylated by sphingosine kinase type 2. FEBS Lett. 2003;554:189–93.

    PubMed  CAS  Google Scholar 

  97. Ishii I, et al. Marked perinatal lethality and cellular signaling deficits in mice null for the two sphingosine 1-phosphate (S1P) receptors, S1P(2)/LP(B2)/EDG-5 and S1P(3)/LP(B3)/EDG-3. J Biol Chem. 2002;277:25152–9.

    PubMed  CAS  Google Scholar 

  98. MacLennan AJ, et al. An essential role for the H218/AGR16/Edg-5/LP(B2) sphingosine 1-phosphate receptor in neuronal excitability. Eur J Neurosci. 2001;14:203–9.

    PubMed  CAS  Google Scholar 

  99. Ishii I, et al. Selective loss of sphingosine 1-phosphate signaling with no obvious phenotypic abnormality in mice lacking its G protein-coupled receptor, LP(B3)/EDG-3. J Biol Chem. 2001;276:33697–704.

    PubMed  CAS  Google Scholar 

  100. Lorenz JN, Arend LJ, Robitz R, Paul RJ, MacLennan AJ. Vascular dysfunction in S1P2 sphingosine 1-phosphate receptor knockout mice. Am J Physiol Regul Integr Comp Physiol. 2007;292:R440–6.

    PubMed  CAS  Google Scholar 

  101. MacLennan AJ, et al. The S1P2 sphingosine 1-phosphate receptor is essential for auditory and vestibular function. Hear Res. 2006;220:38–48.

    PubMed  CAS  Google Scholar 

  102. Sanna MG, et al. Enhancement of capillary leakage and restoration of lymphocyte egress by a chiral S1P1 antagonist in vivo. Nat Chem Biol. 2006;2:434–41.

    PubMed  CAS  Google Scholar 

  103. Foss FW Jr, et al. Synthesis and biological evaluation of gamma-aminophosphonates as potent, subtype-selective sphingosine 1-phosphate receptor agonists and antagonists. Bioorg Med Chem. 2007;15:663–77.

    PubMed  CAS  Google Scholar 

  104. Cinamon G, et al. Sphingosine 1-phosphate receptor 1 promotes B cell localization in the splenic marginal zone. Nat Immunol. 2004;5:713–20.

    PubMed  CAS  Google Scholar 

  105. Vora KA, et al. Sphingosine 1-phosphate receptor agonist FTY720-phosphate causes marginal zone B cell displacement. J Leukoc Biol. 2005;78:471–80.

    PubMed  CAS  Google Scholar 

  106. Kunisawa J, et al. Sphingosine 1-phosphate-dependent trafficking of peritoneal B cells requires functional NFkappaB-inducing kinase in stromal cells. Blood. 2008;111:4646–52.

    PubMed  CAS  Google Scholar 

  107. Kunisawa J, et al. Sphingosine 1-phosphate regulates peritoneal B-cell trafficking for subsequent intestinal IgA production. Blood. 2007;109:3749–56.

    PubMed  CAS  Google Scholar 

  108. Singer II, et al. Sphingosine-1-phosphate agonists increase macrophage homing, lymphocyte contacts, and endothelial junctional complex formation in murine lymph nodes. J Immunol. 2005;175:7151–61.

    PubMed  CAS  Google Scholar 

  109. Wei SH, et al. Sphingosine 1-phosphate type 1 receptor agonism inhibits transendothelial migration of medullary T cells to lymphatic sinuses. Nat Immunol. 2005;6:1228–35.

    PubMed  CAS  Google Scholar 

  110. Ledgerwood LG, et al. The sphingosine 1-phosphate receptor 1 causes tissue retention by inhibiting the entry of peripheral tissue T lymphocytes into afferent lymphatics. Nat Immunol. 2008;9:42–53.

    PubMed  CAS  Google Scholar 

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Davis, M.D., Kehrl, J.H. The influence of sphingosine-1-phosphate receptor signaling on lymphocyte trafficking: How a bioactive lipid mediator grew up from an “immature” vascular maturation factor to a “mature” mediator of lymphocyte behavior and function. Immunol Res 43, 187–197 (2009). https://doi.org/10.1007/s12026-008-8066-5

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