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S1P Control of Endothelial Integrity

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Sphingosine-1-Phosphate Signaling in Immunology and Infectious Diseases

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 378))

Abstract

Sphingosine 1-phosphate (S1P), a lipid mediator produced by sphingolipid metabolism, promotes endothelial cell spreading, vascular maturation/stabilization, and barrier function. S1P is present at high concentrations in the circulatory system, whereas in tissues its levels are low. This so-called vascular S1P gradient is essential for S1P to regulate much physiological and pathophysiological progress such as the modulation of vascular permeability. Cellular sources of S1P in blood has only recently begun to be identified. In this review, we summarize the current understanding of S1P in regulating vascular integrity. In particular, we discuss the recent discovery of the endothelium-protective functions of HDL-bound S1P which is chaperoned by apolipoprotein M.

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Abbreviations

AJ:

Adherens junctions

AKI:

Acute kidney injury

ALI:

Acute lung injury

ApoM:

Apolipoprotein M

BAL:

Bronchoalveolar lavage

EC:

Endothelial cells

eNOS:

Endothelial nitric oxide synthase

GEFs:

Guanine nucleotide exchange factors

GJ:

Gap junctions

HDL:

High-density lipoprotein

HUVEC:

Human umbilical vein endothelial cells

I/R:

Ischemia-reperfusion

JAM:

Junctional adhesion molecules

LDL:

Low-density lipoprotein

LPP3:

Lysophospholipid phosphatase 3

LPs:

Lysophospholipids

LPS:

Lipopolysaccharide

MLC:

Myosin light chain

MLCK:

Myosin light chain kinase

PAF:

Platelet-activating factor

PE:

Phosphatidylethanolamine

PECAM-1:

Platelet-endothelial cell adhesion molecule-1

RBC:

Red blood cells

S1P:

Sphingosine 1-phosphate

SM:

Sphingomyelin

Spns2:

Spinster 2

SPP:

S1P phosphatases

TER:

Transmonolayer electrical resistance

TJ:

Tight junctions

VE-cadherin:

Vascular endothelial cadherin

VLDL:

Very low-density lipoprotein

ZO:

Zona occludens proteins

References

  • Allende ML, Sasaki T, Kawai H, Olivera A, Mi Y, van Echten-Deckert G, Hajdu R, Rosenbach M, Keohane CA, Mandala S, Spiegel S, Proia RL (2004) Mice deficient in sphingosine kinase 1 are rendered lymphopenic by FTY720. J Biol Chem 279(50):52487–52492. doi:10.1074/jbc.M406512200, M406512200 [pii]

    Google Scholar 

  • Ancellin N, Colmont C, Su J, Li Q, Mittereder N, Chae SS, Stefansson S, Liau G, Hla T (2002) Extracellular export of sphingosine kinase-1 enzyme. Sphingosine 1-phosphate generation and the induction of angiogenic vascular maturation. J Biol Chem 277(8):6667–6675. doi:10.1074/jbc.M102841200, M102841200 [pii]

    Google Scholar 

  • Anelli V, Bassi R, Tettamanti G, Viani P, Riboni L (2005) Extracellular release of newly synthesized sphingosine-1-phosphate by cerebellar granule cells and astrocytes. J Neurochem 92(5):1204–1215. doi:10.1111/j.1471-4159.2004.02955.x, JNC2955 [pii]

    Google Scholar 

  • Arce FT, Whitlock JL, Birukova AA, Birukov KG, Arnsdorf MF, Lal R, Garcia JG, Dudek SM (2008) Regulation of the micromechanical properties of pulmonary endothelium by S1P and thrombin: role of cortactin. Biophys J 95(2):886–894. doi:10.1529/biophysj.107.127167, S0006-3495(08)70263-7 [pii]

    Google Scholar 

  • Argraves KM, Gazzolo PJ, Groh EM, Wilkerson BA, Matsuura BS, Twal WO, Hammad SM, Argraves WS (2008) High density lipoprotein-associated sphingosine 1-phosphate promotes endothelial barrier function. J Biol Chem 283(36):25074–25081. doi:10.1074/jbc.M801214200, M801214200 [pii]

    Google Scholar 

  • Argraves KM, Sethi AA, Gazzolo PJ, Wilkerson BA, Remaley AT, Tybjaerg-Hansen A, Nordestgaard BG, Yeatts SD, Nicholas KS, Barth JL, Argraves WS (2011) S1P, dihydro-S1P and C24:1-ceramide levels in the HDL-containing fraction of serum inversely correlate with occurrence of ischemic heart disease. Lipids Health Dis 10:70. doi:10.1186/1476-511X-10-70, 1476-511X-10-70 [pii]

  • Bandhuvula P, Saba JD (2007) Sphingosine-1-phosphate lyase in immunity and cancer: silencing the siren. Trends Mol Med 13(5):210–217. doi:10.1016/j.molmed.2007.03.005, S1471-4914(07)00060-3 [pii]

    Google Scholar 

  • Bassi R, Anelli V, Giussani P, Tettamanti G, Viani P, Riboni L (2006) Sphingosine-1-phosphate is released by cerebellar astrocytes in response to bFGF and induces astrocyte proliferation through Gi-protein-coupled receptors. Glia 53(6):621–630. doi:10.1002/glia.20324

    Google Scholar 

  • Bazzoni G, Dejana E (2004) Endothelial cell-to-cell junctions: molecular organization and role in vascular homeostasis. Physiol Rev 84(3):869–901. doi:10.1152/physrev.00035.2003, 84/3/869 [pii]

    Google Scholar 

  • Belvitch P, Dudek SM (2012) Role of FAK in S1P-regulated endothelial permeability. Microvasc Res 83(1):22–30. doi:10.1016/j.mvr.2011.08.012, S0026-2862(11)00158-0 [pii]

    Google Scholar 

  • Berdyshev EV, Gorshkova I, Skobeleva A, Bittman R, Lu X, Dudek SM, Mirzapoiazova T, Garcia JG, Natarajan V (2009) FTY720 inhibits ceramide synthases and up-regulates dihydrosphingosine 1-phosphate formation in human lung endothelial cells. J Biol Chem 284(9):5467–5477. doi:10.1074/jbc.M805186200, M805186200 [pii]

    Google Scholar 

  • Berdyshev EV, Gorshkova IA, Garcia JG, Natarajan V, Hubbard WC (2005) Quantitative analysis of sphingoid base-1-phosphates as bisacetylated derivatives by liquid chromatography-tandem mass spectrometry. Anal Biochem 339(1):129–136. doi:10.1016/j.ab.2004.12.006, S0003-2697(04)00975-3 [pii]

    Google Scholar 

  • Blaho VA, Hla T (2011) Regulation of mammalian physiology, development, and disease by the sphingosine 1-phosphate and lysophosphatidic acid receptors. Chem Rev 111(10):6299–6320. doi:10.1021/cr200273u

    Google Scholar 

  • Blondeau N, Lai Y, Tyndall S, Popolo M, Topalkara K, Pru JK, Zhang L, Kim H, Liao JK, Ding K, Waeber C (2007) Distribution of sphingosine kinase activity and mRNA in rodent brain. J Neurochem 103(2):509–517. doi:10.1111/j.1471-4159.2007.04755.x, JNC4755 [pii]

    Google Scholar 

  • Bode C, Sensken SC, Peest U, Beutel G, Thol F, Levkau B, Li Z, Bittman R, Huang T, Tolle M, van der Giet M, Graler MH (2010) Erythrocytes serve as a reservoir for cellular and extracellular sphingosine 1-phosphate. J Cell Biochem 109(6):1232–1243. doi:10.1002/jcb.22507

    Google Scholar 

  • Bogatcheva NV, Verin AD (2008) The role of cytoskeleton in the regulation of vascular endothelial barrier function. Microvasc Res 76(3):202–207. doi:10.1016/j.mvr.2008.06.003, S0026-2862(08)00095-2 [pii]

    Google Scholar 

  • Caligan TB, Peters K, Ou J, Wang E, Saba J, Merrill AH, Jr. (2000) A high-performance liquid chromatographic method to measure sphingosine 1-phosphate and related compounds from sphingosine kinase assays and other biological samples. Anal Biochem 281(1):36–44. doi:10.1006/abio.2000.4555, S0003-2697(00)94555-X [pii]

    Google Scholar 

  • Camerer E, Regard JB, Cornelissen I, Srinivasan Y, Duong DN, Palmer D, Pham TH, Wong JS, Pappu R, Coughlin SR (2009) Sphingosine-1-phosphate in the plasma compartment regulates basal and inflammation-induced vascular leak in mice. J Clin Invest 119(7):1871–1879

    Google Scholar 

  • Carmeliet P, Lampugnani MG, Moons L, Breviario F, Compernolle V, Bono F, Balconi G, Spagnuolo R, Oosthuyse B, Dewerchin M, Zanetti A, Angellilo A, Mattot V, Nuyens D, Lutgens E, Clotman F, de Ruiter MC, Gittenberger-de Groot A, Poelmann R, Lupu F, Herbert JM, Collen D, Dejana E (1999) Targeted deficiency or cytosolic truncation of the VE-cadherin gene in mice impairs VEGF-mediated endothelial survival and angiogenesis. Cell 98(2):147–157. doi:S0092-8674(00)81010-7 [pii]

    Google Scholar 

  • Cattelino A, Liebner S, Gallini R, Zanetti A, Balconi G, Corsi A, Bianco P, Wolburg H, Moore R, Oreda B, Kemler R, Dejana E (2003) The conditional inactivation of the beta-catenin gene in endothelial cells causes a defective vascular pattern and increased vascular fragility. J Cell Biol 162(6):1111–1122. doi:10.1083/jcb.200212157, jcb.200212157 [pii]

    Google Scholar 

  • Christoffersen C, Ahnstrom J, Axler O, Christensen EI, Dahlback B, Nielsen LB (2008) The signal peptide anchors apolipoprotein M in plasma lipoproteins and prevents rapid clearance of apolipoprotein M from plasma. J Biol Chem 283(27):18765–18772. doi:10.1074/jbc.M800695200, M800695200 [pii]

    Google Scholar 

  • Christoffersen C, Nielsen LB, Axler O, Andersson A, Johnsen AH, Dahlback B (2006) Isolation and characterization of human apolipoprotein M-containing lipoproteins. J Lipid Res 47(8):1833–1843. doi:10.1194/jlr.M600055-JLR200, M600055-JLR200 [pii]

    Google Scholar 

  • Christoffersen C, Obinata H, Kumaraswamy SB, Galvani S, Ahnstrom J, Sevvana M, Egerer-Sieber C, Muller YA, Hla T, Nielsen LB, Dahlback B (2011) Endothelium-protective sphingosine-1-phosphate provided by HDL-associated apolipoprotein M. Proc Natl Acad Sci USA 108(23):9613–9618. doi:10.1073/pnas.1103187108, 1103187108 [pii]

    Google Scholar 

  • Chun J, Goetzl EJ, Hla T, Igarashi Y, Lynch KR, Moolenaar W, Pyne S, Tigyi G (2002) International Union of Pharmacology. XXXIV. Lysophospholipid receptor nomenclature. Pharmacol Rev 54(2):265–269

    Google Scholar 

  • Chun J, Hla T, Lynch KR, Spiegel S, Moolenaar WH (2010) International Union of Basic and Clinical Pharmacology. LXXVIII. Lysophospholipid receptor nomenclature. Pharmacol Rev 62(4):579–587. doi:10.1124/pr.110.003111

    Google Scholar 

  • Corada M, Mariotti M, Thurston G, Smith K, Kunkel R, Brockhaus M, Lampugnani MG, Martin-Padura I, Stoppacciaro A, Ruco L, McDonald DM, Ward PA, Dejana E (1999) Vascular endothelial-cadherin is an important determinant of microvascular integrity in vivo. Proc Natl Acad Sci USA 96(17):9815–9820

    Google Scholar 

  • Cui H, Okamoto Y, Yoshioka K, Du W, Takuwa N, Zhang W, Asano M, Shibamoto T, Takuwa Y (2013) Sphingosine-1-phosphate receptor 2 protects against anaphylactic shock through suppression of endothelial nitric oxide synthase in mice. J Allergy Clin Immunol. doi:10.1016/j.jaci.2013.07.026, S0091-6749(13)01151-2 [pii]

  • de Bisschop MB, Bellou A (2012) Anaphylaxis. Curr Opin Crit Care 18(4):308–317. doi:10.1097/MCC.0b013e3283557a63

  • Dejana E (2004) Endothelial cell-cell junctions: happy together. Nat Rev Mol Cell Biol 5(4):261–270. doi:10.1038/nrm1357, nrm1357 [pii]

    Google Scholar 

  • Dudek SM, Camp SM, Chiang ET, Singleton PA, Usatyuk PV, Zhao Y, Natarajan V, Garcia JG (2007) Pulmonary endothelial cell barrier enhancement by FTY720 does not require the S1P1 receptor. Cell Sig 19(8):1754–1764. doi:10.1016/j.cellsig.2007.03.011, S0898-6568(07)00098-8 [pii]

    Google Scholar 

  • Dudek SM, Jacobson JR, Chiang ET, Birukov KG, Wang P, Zhan X, Garcia JG (2004) Pulmonary endothelial cell barrier enhancement by sphingosine 1-phosphate: roles for cortactin and myosin light chain kinase. J Biol Chem 279(23):24692–24700. doi:10.1074/jbc.M313969200, M313969200 [pii]

    Google Scholar 

  • Edsall LC, Spiegel S (1999) Enzymatic measurement of sphingosine 1-phosphate. Anal Biochem 272(1):80–86. doi:10.1006/abio.1999.4157, S0003-2697(99)94157-X [pii]

    Google Scholar 

  • Egom EE (2013) Sphingosine-1-phosphate signalling as a therapeutic target for patients with abnormal glucose metabolism and ischaemic heart disease. J Cardiovasc Med (Hagerstown). (in press). doi:10.2459/JCM.0b013e3283639755

  • English D, Welch Z, Kovala AT, Harvey K, Volpert OV, Brindley DN, Garcia JG (2000) Sphingosine 1-phosphate released from platelets during clotting accounts for the potent endothelial cell chemotactic activity of blood serum and provides a novel link between hemostasis and angiogenesis. FASEB J 14(14):2255–2265. doi:10.1096/fj.00-0134com, 14/14/2255 [pii]

    Google Scholar 

  • Fukuhara S, Simmons S, Kawamura S, Inoue A, Orba Y, Tokudome T, Sunden Y, Arai Y, Moriwaki K, Ishida J, Uemura A, Kiyonari H, Abe T, Fukamizu A, Hirashima M, Sawa H, Aoki J, Ishii M, Mochizuki N (2012) The sphingosine-1-phosphate transporter Spns2 expressed on endothelial cells regulates lymphocyte trafficking in mice. J Clin Invest 122(4):1416–1426. doi:10.1172/JCI60746, 60746 [pii]

    Google Scholar 

  • Gaengel K, Niaudet C, Hagikura K, Lavina B, Muhl L, Hofmann JJ, Ebarasi L, Nystrom S, Rymo S, Chen LL, Pang MF, Jin Y, Raschperger E, Roswall P, Schulte D, Benedito R, Larsson J, Hellstrom M, Fuxe J, Uhlen P, Adams R, Jakobsson L, Majumdar A, Vestweber D, Uv A, Betsholtz C (2012) The sphingosine-1-phosphate receptor S1PR1 restricts sprouting angiogenesis by regulating the interplay between VE-cadherin and VEGFR2. Dev Cell 23(3):587–599. doi:10.1016/j.devcel.2012.08.005, S1534-5807(12)00373-5 [pii]

    Google Scholar 

  • Garcia JG, Liu F, Verin AD, Birukova A, Dechert MA, Gerthoffer WT, Bamberg JR, English D (2001) Sphingosine 1-phosphate promotes endothelial cell barrier integrity by Edg-dependent cytoskeletal rearrangement. J Clin Invest 108(5):689–701. doi:10.1172/JCI12450

    Google Scholar 

  • Hait NC, Oskeritzian CA, Paugh SW, Milstien S, Spiegel S (2006) Sphingosine kinases, sphingosine 1-phosphate, apoptosis and diseases. Biochim Biophys Acta 1758(12):2016–2026. doi:10.1016/j.bbamem.2006.08.007, S0005-2736(06)00313-0 [pii]

  • Hanel P, Andreani P, Graler MH (2007) Erythrocytes store and release sphingosine 1-phosphate in blood. FASEB J 21(4):1202–1209. doi:10.1096/fj.06-7433com, fj.06-7433com [pii]

    Google Scholar 

  • Hannun YA, Obeid LM (2008) Principles of bioactive lipid signalling: lessons from sphingolipids. Nat Rev Mol Cell Biol 9(2):139–150. doi:10.1038/nrm2329, nrm2329 [pii]

    Google Scholar 

  • Hanson MA, Roth CB, Jo E, Griffith MT, Scott FL, Reinhart G, Desale H, Clemons B, Cahalan SM, Schuerer SC, Sanna MG, Han GW, Kuhn P, Rosen H, Stevens RC (2012) Crystal structure of a lipid G protein-coupled receptor. Science 335(6070):851–855. doi:10.1126/science.1215904, 335/6070/851 [pii]

    Google Scholar 

  • Herzog BH, Fu J, Wilson SJ, Hess PR, Sen A, McDaniel JM, Pan Y, Sheng M, Yago T, Silasi-Mansat R, McGee S, May F, Nieswandt B, Morris AJ, Lupu F, Coughlin SR, McEver RP, Chen H, Kahn ML, Xia L (2013) Podoplanin maintains high endothelial venule integrity by interacting with platelet CLEC-2. Nature 502 (7469):105--109. doi:10.1038/nature12501

  • Hisano Y, Kobayashi N, Yamaguchi A, Nishi T (2012) Mouse SPNS2 functions as a sphingosine-1-phosphate transporter in vascular endothelial cells. PLoS One 7(6):e38941. doi:10.1371/journal.pone.0038941, PONE-D-12-07568 [pii]

  • Hla T (2003) Signaling and biological actions of sphingosine 1-phosphate. Pharmacol Res 47(5):401–407. doi:S104366180300046X [pii]

    Google Scholar 

  • Hla T, Lee MJ, Ancellin N, Paik JH, Kluk MJ (2001) Lysophospholipids–receptor revelations. Science 294(5548):1875–1878. doi:10.1126/science.1065323, 294/5548/1875 [pii]

    Google Scholar 

  • Hla T, Venkataraman K, Michaud J (2008) The vascular S1P gradient-cellular sources and biological significance. Biochim Biophys Acta 1781(9):477–482. doi:10.1016/j.bbalip.2008.07.003, S1388-1981(08)00132-7 [pii]

    Google Scholar 

  • Igarashi N, Okada T, Hayashi S, Fujita T, Jahangeer S, Nakamura S (2003) Sphingosine kinase 2 is a nuclear protein and inhibits DNA synthesis. J Biol Chem 278(47):46832–46839. doi:10.1074/jbc.M306577200, M306577200 [pii]

    Google Scholar 

  • Ito K, Anada Y, Tani M, Ikeda M, Sano T, Kihara A, Igarashi Y (2007) Lack of sphingosine 1-phosphate-degrading enzymes in erythrocytes. Biochem Biophys Res Commun 357(1):212–217. doi:10.1016/j.bbrc.2007.03.123, S0006-291X(07)00607-9 [pii]

    Google Scholar 

  • Jessup W (2008) Lipid metabolism: sources and stability of plasma sphingosine-1-phosphate. Curr Opin Lipidol 19(5):543–544. doi:10.1097/MOL.0b013e32830f4a90, 00041433-200810000-00017 [pii]

    Google Scholar 

  • Jiang X, Han X (2006) Characterization and direct quantitation of sphingoid base-1-phosphates from lipid extracts: a shotgun lipidomics approach. J Lipid Res 47(8):1865–1873. doi:10.1194/jlr.D600012-JLR200, D600012-JLR200 [pii]

    Google Scholar 

  • Jung B, Obinata H, Galvani S, Mendelson K, Ding BS, Skoura A, Kinzel B, Brinkmann V, Rafii S, Evans T, Hla T (2012) Flow-regulated endothelial S1P receptor-1 signaling sustains vascular development. Dev Cell 23(3):600–610. doi:10.1016/j.devcel.2012.07.015, S1534-5807(12)00334-6 [pii]

    Google Scholar 

  • Karuna R, Park R, Othman A, Holleboom AG, Motazacker MM, Sutter I, Kuivenhoven JA, Rohrer L, Matile H, Hornemann T, Stoffel M, Rentsch KM, von Eckardstein A (2011) Plasma levels of sphingosine-1-phosphate and apolipoprotein M in patients with monogenic disorders of HDL metabolism. Atherosclerosis 219(2):855–863. doi:10.1016/j.atherosclerosis.2011.08.049, S0021-9150(11)00853-7 [pii]

    Google Scholar 

  • Kawahara A, Nishi T, Hisano Y, Fukui H, Yamaguchi A, Mochizuki N (2009) The sphingolipid transporter spns2 functions in migration of zebrafish myocardial precursors. Science 323(5913):524–527. doi:10.1126/science.1167449, 1167449 [pii]

    Google Scholar 

  • Krump-Konvalinkova V, Chwalla I, Siess W (2008) FTY720 inhibits S1P-mediated endothelial healing: relationship to S1P1-receptor surface expression. Biochem Biophys Res Commun 370(4):603–608. doi:10.1016/j.bbrc.2008.03.144, S0006-291X(08)00637-2 [pii]

    Google Scholar 

  • Krump-Konvalinkova V, Yasuda S, Rubic T, Makarova N, Mages J, Erl W, Vosseler C, Kirkpatrick CJ, Tigyi G, Siess W (2005) Stable knock-down of the sphingosine 1-phosphate receptor S1P1 influences multiple functions of human endothelial cells. Arterioscler Thromb Vasc Biol 25(3):546–552. doi:10.1161/01.ATV.0000154360.36106.d9, 01.ATV.0000154360.36106.d9 [pii]

    Google Scholar 

  • Kuhn R, Schwenk F, Aguet M, Rajewsky K (1995) Inducible gene targeting in mice. Science 269(5229):1427–1429

    Google Scholar 

  • Kurano M, Tsukamoto K, Ohkawa R, Hara M, Iino J, Kageyama Y, Ikeda H, Yatomi Y (2013) Liver involvement in sphingosine 1-phosphate dynamism revealed by adenoviral hepatic overexpression of apolipoprotein M. Atherosclerosis 229(1):102–109. doi:10.1016/j.atherosclerosis.2013.04.024, S0021-9150(13)00266-9 [pii]

    Google Scholar 

  • Le Stunff H, Peterson C, Thornton R, Milstien S, Mandala SM, Spiegel S (2002) Characterization of murine sphingosine-1-phosphate phosphohydrolase. J Biol Chem 277(11):8920–8927. doi:10.1074/jbc.M109968200, M109968200 [pii]

    Google Scholar 

  • Lee JF, Gordon S, Estrada R, Wang L, Siow DL, Wattenberg BW, Lominadze D, Lee MJ (2009) Balance of S1P1 and S1P2 signaling regulates peripheral microvascular permeability in rat cremaster muscle vasculature. Am J Physiol Heart Circ Physiol 296(1):H33–42. doi:10.1152/ajpheart.00097.2008, 00097.2008 [pii]

    Google Scholar 

  • Lee JF, Zeng Q, Ozaki H, Wang L, Hand AR, Hla T, Wang E, Lee MJ (2006) Dual roles of tight junction-associated protein, zonula occludens-1, in sphingosine 1-phosphate-mediated endothelial chemotaxis and barrier integrity. J Biol Chem 281(39):29190–29200. doi:10.1074/jbc.M604310200, M604310200 [pii]

    Google Scholar 

  • Lee MJ, Thangada S, Claffey KP, Ancellin N, Liu CH, Kluk M, Volpi M, Sha’afi RI, Hla T (1999) Vascular endothelial cell adherens junction assembly and morphogenesis induced by sphingosine-1-phosphate. Cell 99(3):301–312. doi:S0092-8674(00)81661-X [pii]

    Google Scholar 

  • Lee MJ, Van Brocklyn JR, Thangada S, Liu CH, Hand AR, Menzeleev R, Spiegel S, Hla T (1998) Sphingosine-1-phosphate as a ligand for the G protein-coupled receptor EDG-1. Science 279(5356):1552–1555

    Google Scholar 

  • Lee SY, Kim DH, Sung SA, Kim MG, Cho WY, Kim HK, Jo SK (2011) Sphingosine-1-phosphate reduces hepatic ischaemia/reperfusion-induced acute kidney injury through attenuation of endothelial injury in mice. Nephrology (Carlton) 16(2):163–173. doi:10.1111/j.1440-1797.2010.01386.x

  • Matthay MA, Ware LB, Zimmerman GA (2012) The acute respiratory distress syndrome. J Clin Invest 122(8):2731–2740. doi:10.1172/JCI60331, 60331 [pii]

    Google Scholar 

  • McVerry BJ, Peng X, Hassoun PM, Sammani S, Simon BA, Garcia JG (2004) Sphingosine 1-phosphate reduces vascular leak in murine and canine models of acute lung injury. Am J Respir Crit Care Med 170(9):987–993. doi:10.1164/rccm.200405-684OC, 200405-684OC [pii]

    Google Scholar 

  • Mendoza A, Breart B, Ramos-Perez WD, Pitt LA, Gobert M, Sunkara M, Lafaille JJ, Morris AJ, Schwab SR (2012) The transporter Spns2 is required for secretion of lymph but not plasma sphingosine-1-phosphate. Cell Rep 2(5):1104–1110. doi:10.1016/j.celrep.2012.09.021, S2211-1247(12)00325-7 [pii]

    Google Scholar 

  • Michel CC, Curry FE (1999) Microvascular permeability. Physiol Rev 79 (3):703-761

    Google Scholar 

  • Min JK, Yoo HS, Lee EY, Lee WJ, Lee YM (2002) Simultaneous quantitative analysis of sphingoid base 1-phosphates in biological samples by o-phthalaldehyde precolumn derivatization after dephosphorylation with alkaline phosphatase. Anal Biochem 303(2):167–175. doi:10.1006/abio.2002.5579 S000326970295579X [pii]

    Google Scholar 

  • Moolenaar WH, Hla T (2012) SnapShot: bioactive lysophospholipids. Cell 148(1–2):378–378 e372. doi:10.1016/j.cell.2012.01.013

    Google Scholar 

  • Moreno-Vinasco L, Jacobson JR, Bonde P, Sammani S, Mirzapoiazova T, Vigneswaran WT, Garcia JGN (2008) Attenuation of rodent lung ischemia-reperfusion injury by sphingosine 1-phosphate. J Organ Dysfunction 4(2):106–114. doi:10.1080/17471060701505289

    Google Scholar 

  • Muller HC, Hocke AC, Hellwig K, Gutbier B, Peters H, Schonrock SM, Tschernig T, Schmiedl A, Hippenstiel S, N’Guessan PD, Rosseau S, Suttorp N, Witzenrath M (2011) The Sphingosine-1 Phosphate receptor agonist FTY720 dose dependently affected endothelial integrity in vitro and aggravated ventilator-induced lung injury in mice. Pulm Pharmacol Ther 24(4):377–385. doi:10.1016/j.pupt.2011.01.017, S1094-5539(11)00039-3 [pii]

  • Mullin JM, Agostino N, Rendon-Huerta E, Thornton JJ (2005) Keynote review: epithelial and endothelial barriers in human disease. Drug Discov Today 10(6):395–408. doi:10.1016/S1359-6446(05)03379-9, S1359644605033799 [pii]

  • Murata N, Sato K, Kon J, Tomura H, Okajima F (2000a) Quantitative measurement of sphingosine 1-phosphate by radioreceptor-binding assay. Anal Biochem 282 (1):115-120. doi:10.1006/abio.2000.4580 S0003-2697(00)94580-9 [pii]

    Google Scholar 

  • Murata N, Sato K, Kon J, Tomura H, Yanagita M, Kuwabara A, Ui M, Okajima F (2000b) Interaction of sphingosine 1-phosphate with plasma components, including lipoproteins, regulates the lipid receptor-mediated actions. Biochem J 352(Pt 3):809–815

    Google Scholar 

  • Nofer JR, van der Giet M, Tolle M, Wolinska I, von Wnuck Lipinski K, Baba HA, Tietge UJ, Godecke A, Ishii I, Kleuser B, Schafers M, Fobker M, Zidek W, Assmann G, Chun J, Levkau B (2004) HDL induces NO-dependent vasorelaxation via the lysophospholipid receptor S1P3. J Clin Invest 113(4):569–581. doi:10.1172/JCI18004

    Google Scholar 

  • Ogawa C, Kihara A, Gokoh M, Igarashi Y (2003) Identification and characterization of a novel human sphingosine-1-phosphate phosphohydrolase, hSPP2. J Biol Chem 278(2):1268–1272. doi:10.1074/jbc.M209514200, M209514200 [pii]

    Google Scholar 

  • Okazaki M, Kreisel F, Richardson SB, Kreisel D, Krupnick AS, Patterson GA, Gelman AE (2007) Sphingosine 1-phosphate inhibits ischemia reperfusion injury following experimental lung transplantation. Am J Transplant 7(4):751–758. doi:10.1111/j.1600-6143.2006.01710.x, AJT1710 [pii]

    Google Scholar 

  • Olivera A, Mizugishi K, Tikhonova A, Ciaccia L, Odom S, Proia RL, Rivera J (2007) The sphingosine kinase-sphingosine-1-phosphate axis is a determinant of mast cell function and anaphylaxis. Immunity 26(3):287–297. doi:10.1016/j.immuni.2007.02.008, S1074-7613(07)00174-4 [pii]

    Google Scholar 

  • Olivera A, Spiegel S (1993) Sphingosine-1-phosphate as second messenger in cell proliferation induced by PDGF and FCS mitogens. Nature 365(6446):557–560. doi:10.1038/365557a0

    Google Scholar 

  • Oo ML, Chang SH, Thangada S, Wu MT, Rezaul K, Blaho V, Hwang SI, Han DK, Hla T (2011) Engagement of S1P(1)-degradative mechanisms leads to vascular leak in mice. J Clin Invest 121(6):2290–2300. doi:10.1172/JCI45403, 45403 [pii]

    Google Scholar 

  • Oskeritzian CA, Price MM, Hait NC, Kapitonov D, Falanga YT, Morales JK, Ryan JJ, Milstien S, Spiegel S (2010) Essential roles of sphingosine-1-phosphate receptor 2 in human mast cell activation, anaphylaxis, and pulmonary edema. J Exp Med 207(3):465–474. doi:10.1084/jem.20091513, jem.20091513 [pii]

    Google Scholar 

  • Owen KA, Pixley FJ, Thomas KS, Vicente-Manzanares M, Ray BJ, Horwitz AF, Parsons JT, Beggs HE, Stanley ER, Bouton AH (2007) Regulation of lamellipodial persistence, adhesion turnover, and motility in macrophages by focal adhesion kinase. J Cell Biol 179(6):1275–1287. doi:10.1083/jcb.200708093, jcb.200708093 [pii]

    Google Scholar 

  • Oyama O, Sugimoto N, Qi X, Takuwa N, Mizugishi K, Koizumi J, Takuwa Y (2008) The lysophospholipid mediator sphingosine-1-phosphate promotes angiogenesis in vivo in ischaemic hindlimbs of mice. Cardiovasc Res 78(2):301–307. doi:10.1093/cvr/cvn002, cvn002 [pii]

    Google Scholar 

  • Paik JH, Chae S, Lee MJ, Thangada S, Hla T (2001) 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 276(15):11830–11837. doi:10.1074/jbc.M009422200, M009422200 [pii]

    Google Scholar 

  • Pappu R, Schwab SR, Cornelissen I, Pereira JP, Regard JB, Xu Y, Camerer E, Zheng YW, Huang Y, Cyster JG, Coughlin SR (2007) Promotion of lymphocyte egress into blood and lymph by distinct sources of sphingosine-1-phosphate. Science 316(5822):295–298. doi:10.1126/science.1139221, 1139221 [pii]

    Google Scholar 

  • Peng X, Hassoun PM, Sammani S, McVerry BJ, Burne MJ, Rabb H, Pearse D, Tuder RM, Garcia JG (2004) Protective effects of sphingosine 1-phosphate in murine endotoxin-induced inflammatory lung injury. Am J Respir Crit Care Med 169(11):1245–1251. doi:10.1164/rccm.200309-1258OC, 200309-1258OC [pii]

    Google Scholar 

  • Pitman MR, Woodcock JM, Lopez AF, Pitson SM (2012) Molecular targets of FTY720 (fingolimod). Curr Mol Med 12(10):1207–1219. doi:CMM-EPUB-20120723-1 [pii]

    Google Scholar 

  • Predescu SA, Predescu DN, Malik AB (2007) Molecular determinants of endothelial transcytosis and their role in endothelial permeability. Am J Physiol Lung Cell Mol Physiol 293(4):L823–842. doi:10.1152/ajplung.00436.2006, 00436.2006 [pii]

    Google Scholar 

  • Sammani S, Moreno-Vinasco L, Mirzapoiazova T, Singleton PA, Chiang ET, Evenoski CL, Wang T, Mathew B, Husain A, Moitra J, Sun X, Nunez L, Jacobson JR, Dudek SM, Natarajan V, Garcia JG (2010) Differential effects of sphingosine 1-phosphate receptors on airway and vascular barrier function in the murine lung. Am J Respir Cell Mol Biol 43(4):394–402. doi:10.1165/rcmb.2009-0223OC, 2009-0223OC [pii]

    Google Scholar 

  • Sanchez T, Estrada-Hernandez T, Paik JH, Wu MT, Venkataraman K, Brinkmann V, Claffey K, Hla T (2003) Phosphorylation and action of the immunomodulator FTY720 inhibits vascular endothelial cell growth factor-induced vascular permeability. J Biol Chem 278(47):47281–47290. doi:10.1074/jbc.M306896200, M306896200 [pii]

    Google Scholar 

  • Sanchez T, Skoura A, Wu MT, Casserly B, Harrington EO, Hla T (2007) Induction of vascular permeability by the sphingosine-1-phosphate receptor-2 (S1P2R) and its downstream effectors ROCK and PTEN. Arterioscler Thromb Vasc Biol 27(6):1312–1318. doi:10.1161/ATVBAHA.107.143735, ATVBAHA.107.143735 [pii]

  • Seal JB, Gewertz BL (2005) Vascular dysfunction in ischemia-reperfusion injury. Ann Vasc Surg 19(4):572–584. doi:10.1007/s10016-005-4616-7

    Google Scholar 

  • Shea BS, Brooks SF, Fontaine BA, Chun J, Luster AD, Tager AM (2010) Prolonged exposure to sphingosine 1-phosphate receptor-1 agonists exacerbates vascular leak, fibrosis, and mortality after lung injury. Am J Respir Cell Mol Biol 43(6):662–673. doi:10.1165/rcmb.2009-0345OC, 2009-0345OC [pii]

    Google Scholar 

  • Shikata Y, Birukov KG, Garcia JG (2003) S1P induces FA remodeling in human pulmonary endothelial cells: role of Rac, GIT1, FAK, and paxillin. J Appl Physiol 94(3):1193–1203. doi:10.1152/japplphysiol.00690.2002, 00690.2002 [pii]

    Google Scholar 

  • Shivdasani RA, Rosenblatt MF, Zucker-Franklin D, Jackson CW, Hunt P, Saris CJ, Orkin SH (1995) Transcription factor NF-E2 is required for platelet formation independent of the actions of thrombopoietin/MGDF in megakaryocyte development. Cell 81(5):695–704. doi:0092-8674(95)90531-6 [pii]

    Google Scholar 

  • Spiering D, Hodgson L (2011) Dynamics of the Rho-family small GTPases in actin regulation and motility. Cell Adh Migr 5(2):170–180. doi:14403 [pii]

    Google Scholar 

  • Szczepaniak WS, Zhang Y, Hagerty S, Crow MT, Kesari P, Garcia JG, Choi AM, Simon BA, McVerry BJ (2008) Sphingosine 1-phosphate rescues canine LPS-induced acute lung injury and alters systemic inflammatory cytokine production in vivo. Transl Res 152(5):213–224. doi:10.1016/j.trsl.2008.09.002, S1931-5244(08)00225-9 [pii]

  • Takashima S (2009) Phosphorylation of myosin regulatory light chain by myosin light chain kinase, and muscle contraction. Circ J 73(2):208–213. doi:JST.JSTAGE/circj/CJ-08-1041 [pii]

    Google Scholar 

  • Tani M, Sano T, Ito M, Igarashi Y (2005) Mechanisms of sphingosine and sphingosine 1-phosphate generation in human platelets. J Lipid Res 46(11):2458–2467. doi:10.1194/jlr.M500268-JLR200, M500268-JLR200 [pii]

    Google Scholar 

  • Venkataraman K, Lee YM, Michaud J, Thangada S, Ai Y, Bonkovsky HL, Parikh NS, Habrukowich C, Hla T (2008) Vascular endothelium as a contributor of plasma sphingosine 1-phosphate. Circ Res 102(6):669–676. doi:10.1161/CIRCRESAHA.107.165845, CIRCRESAHA.107.165845 [pii]

    Google Scholar 

  • Venkataraman K, Thangada S, Michaud J, Oo ML, Ai Y, Lee YM, Wu M, Parikh NS, Khan F, Proia RL, Hla T (2006) Extracellular export of sphingosine kinase-1a contributes to the vascular S1P gradient. Biochem J 397(3):461–471. doi:10.1042/BJ20060251

    Google Scholar 

  • Venkiteswaran K, Xiao K, Summers S, Calkins CC, Vincent PA, Pumiglia K, Kowalczyk AP (2002) Regulation of endothelial barrier function and growth by VE-cadherin, plakoglobin, and beta-catenin. Am J Physiol Cell Physiol 283(3):C811–821. doi:10.1152/ajpcell.00417.2001

    Google Scholar 

  • Waeber C (2013) Sphingosine 1-Phosphate (S1P) signaling and the vasculature. In: Lysophospholipid receptors. John Wiley & Sons, Inc., New York, pp 313–347. doi:10.1002/9781118531426.ch15

  • Wilkerson BA, Grass GD, Wing SB, Argraves WS, Argraves KM (2012) Sphingosine 1-phosphate (S1P) carrier-dependent regulation of endothelial barrier: high density lipoprotein (HDL)-S1P prolongs endothelial barrier enhancement as compared with albumin-S1P via effects on levels, trafficking, and signaling of S1P1. J Biol Chem 287(53):44645–44653. doi:10.1074/jbc.M112.423426, M112.423426 [pii]

    Google Scholar 

  • Wojciak-Stothard B, Potempa S, Eichholtz T, Ridley AJ (2001) Rho and Rac but not Cdc42 regulate endothelial cell permeability. J Cell Sci 114 (Pt 7):1343–1355

    Google Scholar 

  • Xu M, Waters CL, Hu C, Wysolmerski RB, Vincent PA, Minnear FL (2007) Sphingosine 1-phosphate rapidly increases endothelial barrier function independently of VE-cadherin but requires cell spreading and Rho kinase. Am J Physiol Cell Physiol 293(4):C1309–1318. doi:10.1152/ajpcell.00014.2007, 00014.2007 [pii]

    Google Scholar 

  • Yatomi Y, Igarashi Y, Yang L, Hisano N, Qi R, Asazuma N, Satoh K, Ozaki Y, Kume S (1997a) Sphingosine 1-phosphate, a bioactive sphingolipid abundantly stored in platelets, is a normal constituent of human plasma and serum. J Biochem 121(5):969–973

    Google Scholar 

  • Yatomi Y, Ozaki Y, Ohmori T, Igarashi Y (2001) Sphingosine 1-phosphate: synthesis and release. Prostaglandins Other Lipid Mediat 64(1–4):107–122

    Google Scholar 

  • Yatomi Y, Welch RJ, Igarashi Y (1997b) Distribution of sphingosine 1-phosphate, a bioactive sphingolipid, in rat tissues. FEBS Lett 404(2–3):173–174. doi:S0014-5793(97)00121-X [pii]

    Google Scholar 

  • Zhang G, Yang L, Kim GS, Ryan K, Lu S, O’Donnell RK, Spokes K, Shapiro N, Aird WC, Kluk MJ, Yano K, Sanchez T (2013) Critical role of sphingosine-1-phosphate receptor 2 (S1PR2) in acute vascular inflammation. Blood 122(3):443–455. doi:10.1182/blood-2012-11-467191, blood-2012-11-467191 [pii]

    Google Scholar 

  • Zhao Y, Gorshkova IA, Berdyshev E, He D, Fu P, Ma W, Su Y, Usatyuk PV, Pendyala S, Oskouian B, Saba JD, Garcia JG, Natarajan V (2011) Protection of LPS-induced murine acute lung injury by sphingosine-1-phosphate lyase suppression. Am J Respir Cell Mol Biol 45(2):426–435. doi:10.1165/rcmb.2010-0422OC, 2010-0422OC [pii]

    Google Scholar 

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  1. Center for Vascular Biology, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, Cornell University, New York, NY, 10165, USA

    Yuquan Xiong & Timothy Hla

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  1. Department of Immunology and Microbial Sciiences, The Scripps Research Institute, La Jolla, California, USA

    Michael B. A. Oldstone

  2. Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California, USA

    Hugh Rosen

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Xiong, Y., Hla, T. (2014). S1P Control of Endothelial Integrity. In: Oldstone, M., Rosen, H. (eds) Sphingosine-1-Phosphate Signaling in Immunology and Infectious Diseases. Current Topics in Microbiology and Immunology, vol 378. Springer, Cham. https://doi.org/10.1007/978-3-319-05879-5_4

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