Sphingolipids in Lung Endothelial Biology and Regulation of Vascular Integrity

Chapter
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 216)

Abstract

Of the multiple and diverse homeostatic events that involve the lung vascular endothelium, participation in preserving vascular integrity and therefore organ function is paramount. We were the first to show that the lipid growth factor and angiogenic factor, sphingosine-1-phosphate, is a critical agonist involved in regulation of human lung vascular barrier function (Garcia et al. J Clin Invest, 2011). Utilizing both in vitro models and preclinical murine, rat, and canine models of acute and chronic inflammatory lung injury, we have shown that S1Ps, as well as multiple S1P analogues such as FTY720 and ftysiponate, serve as protective agents limiting the disruption of the vascular EC monolayer in the pulmonary microcirculation and attenuate parenchymal accumulation of inflammatory cells and high protein containing extravasated fluid, thereby reducing interstitial and alveolar edema. The vasculo-protective mechanism of these therapeutic effects occurs via ligation of specific G-protein-coupled receptors and an intricate interplay of S1P with other factors (such as MAPKS, ROCKs, Rho, Rac1) with rearrangement of the endothelial cytoskeleton to form strong cortical actin rings in the cell periphery and enhanced cell-to-cell and cell-to-matrix tethering dynamics. This cascade leads to reinforcement of focal adhesions and paracellular junctional complexes via cadherin, paxillin, catenins, and zona occludens. S1P through its interaction with Rac and Rho influences the cytoskeletal rearrangement indicated in the later stages of angiogenesis as a stabilizing force, preventing excessive vascular permeability. These properties translate into a therapeutic potential for acute and chronic inflammatory lung injuries. S1P has potential for providing a paradigm shift in the approach to disruption of critical endothelial gatekeeper function, loss of lung vascular integrity, and increased vascular permeability, defining features of acute lung injury (ALI), and may prove to exhibit an intrinsically protective role in the pulmonary vasculature ameliorating agonist- or sepsis-induced pulmonary injury and vascular leakage.

Keywords

Endothelial cells S1P Rac Rho Cytoskeleton 

References

  1. Adyshev DM, Moldobaeva NK, Elangovan VR, Garcia JG, Dudek SM (2011) Differential involvement of ezrin/radixin/moesin proteins in sphingosine 1-phosphate-induced human pulmonary endothelial cell barrier enhancement. Cell Signal 23(12):2086–2096PubMedCrossRefGoogle Scholar
  2. Amano M, Ito M, Kimura K, Fukata Y, Chihara K, Nakano T, Matsuura Y, Kaibuchi K (1996) Phosphorylation and activation of myosin by Rho-associated kinase (Rho-kinase). J Biol Chem 271(34):20246–20249PubMedCrossRefGoogle Scholar
  3. An S, Zheng Y, Bleu T (2000) Sphingosine 1-phosphate-induced cell proliferation, survival, and related signaling events mediated by G protein-coupled receptors Edg3 and Edg5. J Biol Chem 275(1):288–296PubMedCrossRefGoogle Scholar
  4. 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):886–894PubMedCrossRefGoogle Scholar
  5. Argraves KM, Wilkerson BA, Argraves WS, Fleming PA, Obeid LM, Drake CJ (2004) Sphingosine-1-phosphate signaling promotes critical migratory events in vasculogenesis. J Biol Chem 279(48): 50580–50590PubMedCrossRefGoogle Scholar
  6. Bazzoni G, Dejana E (2004) Endothelial cell-to-cell junctions: molecular organization and role in vascular homeostasis. Review. Physiol Rev 84(3):869–901PubMedCrossRefGoogle Scholar
  7. Belvitch P, Dudek SM (2012) Role of FAK in S1P-regulated endothelial permeability. Microvasc Res 83(1):22–30PubMedCrossRefGoogle Scholar
  8. Berdyshev EV, Gorshkova I, Usatyuk P, Kalari S, Zhao Y, Pyne NJ, Pyne S, Sabbadini RA, Garcia JG, Natarajan V (2011) Intracellular S1P generation is essential for S1P-induced motility of human lung endothelial cells: role of sphingosine kinase 1 and S1P lyase. PLoS One 6(1):e16571PubMedCrossRefGoogle Scholar
  9. Birukova AA, Smurova K, Birukov KG, Usatyuk P, Liu F, Kaibuchi K, Ricks-Cord A, Natarajan V, Alieva I, Garcia JG, Verin AD (2004) Microtubule disassembly induces cytoskeletal remodeling and lung vascular barrier dysfunction: role of Rho-dependent mechanisms. J Cell Physiol 201(1):55–70PubMedCrossRefGoogle Scholar
  10. Birukova AA, Malyukova I, Poroyko V, Birukov KG (2007) Paxillin-beta-catenin interactions are involved in Rac/Cdc42-mediated endothelial barrier-protective response to oxidized phospholipids. Am J Physiol Lung Cell Mol Physiol 293(1):L199–L211PubMedCrossRefGoogle Scholar
  11. Bode C, Sensken SC, Peest U, Beutel G, Thol F, Levkau B, Li Z, Bittman R, Huang T, Tölle M, van der Giet M, Gräler MH (2010) Erythrocytes serve as a reservoir for cellular and extracellular sphingosine 1-phosphate. J Cell Biochem 109(6):1232–1243PubMedGoogle Scholar
  12. Boguslawski G, Grogg JR, Welch Z, Ciechanowicz S, Sliva D, Kovala AT, McGlynn P, Brindley DN, Rhoades RA, English D (2002) Migration of vascular smooth muscle cells induced by sphingosine 1-phosphate and related lipids: potential role in the angiogenic response. Exp Cell Res 274(2):264–274PubMedCrossRefGoogle Scholar
  13. Brinkmann V, Davis MD, Heise CE, Albert R, Cottens S, Hof R, Bruns C, Prieschl E, Baumruker T, Hiestand P, Foster CA, Zollinger M, Lynch KR (2002) The immune modulator FTY720 targets sphingosine 1-phosphate receptors. J Biol Chem 277(24):21453–21457PubMedCrossRefGoogle Scholar
  14. Camp SM, Bittman R, Chiang ET, Moreno-Vinasco L, Mirzapoiazova T, Sammani S, Lu X, Sun C, Harbeck M, Roe M, Natarajan V, Garcia JG, Dudek SM (2009) Synthetic analogs of FTY720 [2-amino-2-(2-[4-octylphenyl]ethyl)-1,3-propanediol] differentially regulate pulmonary vascular permeability in vivo and in vitro. J Pharmacol Exp Ther 331(1):54–64PubMedCrossRefGoogle Scholar
  15. 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): 147–157PubMedCrossRefGoogle Scholar
  16. Chae SS, Proia RL, Hla T (2004) Constitutive expression of the S1P1 receptor in adult tissues. Prostaglandins Other Lipid Mediat 73(1–2):141–150PubMedCrossRefGoogle Scholar
  17. 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):9815–9820PubMedCrossRefGoogle Scholar
  18. Donati C, Bruni P (2006) Sphingosine 1-phosphate regulates cytoskeleton dynamics: implications in its biological response. Biochim Biophys Acta 1758(12):2037–2048PubMedCrossRefGoogle Scholar
  19. 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 Signal 19(8):1754–1764PubMedCrossRefGoogle Scholar
  20. Ebnet K, Schulz CU, Meyer Zu Brickwedde MK, Pendl GG, Vestweber D (2000) Junctional adhesion molecule interacts with the PDZ domain-containing proteins AF-6 and ZO-1. J Biol Chem 275(36):27979–27988PubMedGoogle Scholar
  21. English D, Garcia JG, Brindley DN (2001) Platelet-released phospholipids link haemostasis and angiogenesis. Review. Cardiovasc Res 49(3):588–599PubMedCrossRefGoogle Scholar
  22. Furuse M, Itoh M, Hirase T, Nagafuchi A, Yonemura S, Tsukita S, Tsukita S (1994) Direct association of occludin with ZO-1 and its possible involvement in the localization of occludin at tight junctions. J Cell Biol 127(6 Pt 1):1617–1626PubMedCrossRefGoogle Scholar
  23. Futerman AH, Riezman H (2005) The ins and outs of sphingolipid synthesis. Review. Trends Cell Biol 15(6):312–318PubMedCrossRefGoogle Scholar
  24. Fyrst H, Saba JD (2010) An update on sphingosine-1-phosphate and other sphingolipid mediators. Review. Nat Chem Biol 6(7):489–497, Erratum in Nat Chem Biol. 2010;6(9):689PubMedCrossRefGoogle Scholar
  25. 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):689–701PubMedGoogle Scholar
  26. Gon Y, Wood MR, Kiosses WB, Jo E, Sanna MG, Chun J, Rosen H (2005) S1P3 receptor-induced reorganization of epithelial tight junctions compromises lung barrier integrity and is potentiated by TNF. Proc Natl Acad Sci USA 102(26):9270–9275PubMedCrossRefGoogle Scholar
  27. Gosens R, Schaafsma D, Meurs H, Zaagsma J, Nelemans SA (2004) Role of Rho-kinase in maintaining airway smooth muscle contractile phenotype. Eur J Pharmacol 483(1):71–78PubMedCrossRefGoogle Scholar
  28. Hla T (2004) Physiological and pathological actions of sphingosine 1-phosphate. Review. Semin Cell Dev Biol 15(5):513–520PubMedCrossRefGoogle Scholar
  29. Hla T, Brinkmann V (2011) Sphingosine 1-phosphate (S1P): physiology and the effects of S1P receptor modulation. Neurology 76(8 Suppl 3):S3–S8PubMedCrossRefGoogle Scholar
  30. Jacobson JR, Garcia JG (2007) Novel therapies for microvascular permeability in sepsis. Review. Curr Drug Targets 8(4):509–514PubMedCrossRefGoogle Scholar
  31. Jaillard C, Harrison S, Stankoff B, Aigrot MS, Calver AR, Duddy G, Walsh FS, Pangalos MN, Arimura N, Kaibuchi K, Zalc B, Lubetzki C (2005) Edg8/S1P5: an oligodendroglial receptor with dual function on process retraction and cell survival. J Neurosci 25(6):1459–1469PubMedCrossRefGoogle Scholar
  32. Kihara A, Igarashi Y (2008) Production and release of sphingosine 1-phosphate and the phosphorylated form of the immunomodulator FTY720. Review. Biochim Biophys Acta 1781(9):496–502PubMedCrossRefGoogle Scholar
  33. Komarova YA, Mehta D, Malik AB (2007) Dual regulation of endothelial junctional permeability. Review. Sci STKE 412:re8Google Scholar
  34. 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):546–52PubMedCrossRefGoogle Scholar
  35. Lee MJ, Evans M, Hla T (1996) The inducible G protein-coupled receptor edg-1 signals via the G(i)/mitogen-activated protein kinase pathway. J Biol Chem 271(19):11272–11279PubMedCrossRefGoogle Scholar
  36. 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):1552–1555PubMedCrossRefGoogle Scholar
  37. 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):301–312PubMedCrossRefGoogle Scholar
  38. 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):29190–29200PubMedCrossRefGoogle Scholar
  39. Liu Y, Wada R, Yamashita T, Mi Y, Deng CX, Hobson JP, Rosenfeldt HM, Nava VE, Chae SS, Lee MJ, Liu CH, Hla T, Spiegel S, Proia RL (2000) Edg-1, the G protein-coupled receptor for sphingosine-1-phosphate, is essential for vascular maturation. J Clin Invest 106(8):951–961PubMedCrossRefGoogle Scholar
  40. Liu F, Verin AD, Wang P, Day R, Wersto RP, Chrest FJ, English DK, Garcia JG (2001) Differential regulation of sphingosine-1-phosphate- and VEGF-induced endothelial cell chemotaxis. Involvement of G(ialpha2)-linked Rho kinase activity. Am J Respir Cell Mol Biol 24(6):711–719PubMedCrossRefGoogle Scholar
  41. Lucke S, Levkau B (2010) Endothelial functions of sphingosine-1-phosphate. Cell Physiol Biochem 26(1):87–96PubMedCrossRefGoogle Scholar
  42. Mansoor M, Melendez AJ (2008) Recent trials for FTY720 (fingolimod): a new generation of immunomodulators structurally similar to sphingosine. Rev Recent Clin Trials 3(1):62–69PubMedCrossRefGoogle Scholar
  43. Mathew B, Jacobson JR, Berdyshev E, Huang Y, Sun X, Zhao Y, Gerhold LM, Siegler J, Evenoski C, Wang T, Zhou T, Zaidi R, Moreno-Vinasco L, Bittman R, Chen CT, LaRiviere PJ, Sammani S, Lussier YA, Dudek SM, Natarajan V, Weichselbaum RR, Garcia JG (2011) Role of sphingolipids in murine radiation-induced lung injury: protection by sphingosine 1-phosphate analogs. FASEB J 25(10):3388–3400PubMedCrossRefGoogle Scholar
  44. McVerry BJ, Garcia JG (2004) Endothelial cell barrier regulation by sphingosine 1-phosphate. Review. J Cell Biochem 92(6):1075–1085PubMedCrossRefGoogle Scholar
  45. 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):987–993PubMedCrossRefGoogle Scholar
  46. Mehta D, Malik AB (2006) Signaling mechanisms regulating endothelial permeability. Physiol Rev 86(1):279–367, ReviewPubMedCrossRefGoogle Scholar
  47. Mehta D, Tiruppathi C, Sandoval R, Minshall RD, Holinstat M, Malik AB (2002) Modulatory role of focal adhesion kinase in regulating human pulmonary arterial endothelial barrier function. J Physiol 539(Pt 3):779–789PubMedCrossRefGoogle Scholar
  48. Mehta D, Konstantoulaki M, Ahmmed GU, Malik AB (2005) Sphingosine 1-phosphate-induced mobilization of intracellular Ca2+ mediates rac activation and adherens junction assembly in endothelial cells. J Biol Chem 280(17):17320–17328PubMedCrossRefGoogle Scholar
  49. Mitra SK, Hanson DA, Schlaepfer DD (2005) Focal adhesion kinase: in command and control of cell motility. Review. Nat Rev Mol Cell Biol 6(1):56–68PubMedCrossRefGoogle Scholar
  50. Miura Y, Yatomi Y, Rile G, Ohmori T, Satoh K, Ozaki Y (2000) Rho-mediated phosphorylation of focal adhesion kinase and myosin light chain in human endothelial cells stimulated with sphingosine 1-phosphate, a bioactive lysophospholipid released from activated platelets. J Biochem 127(5):909–914PubMedCrossRefGoogle Scholar
  51. Narumiya S, Ishizaki T, Watanabe N (1997) Rho effectors and reorganization of actin cytoskeleton. Review. FEBS Lett 410(1):68–72PubMedCrossRefGoogle Scholar
  52. Ohashi K, Nagata K, Maekawa M, Ishizaki T, Narumiya S, Mizuno K (2000) Rho-associated kinase ROCK activates LIM-kinase 1 by phosphorylation at threonine 508 within the activation loop. J Biol Chem 275(5):3577–3582PubMedCrossRefGoogle Scholar
  53. Ohmori T, Yatomi Y, Okamoto H, Miura Y, Rile G, Satoh K, Ozaki Y (2001) G(i)-mediated Cas tyrosine phosphorylation in vascular endothelial cells stimulated with sphingosine 1-phosphate: possible involvement in cell motility enhancement in cooperation with Rho-mediated pathways. J Biol Chem 276(7):5274–5280PubMedCrossRefGoogle Scholar
  54. 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):1275–1287PubMedCrossRefGoogle Scholar
  55. Paik JH, Skoura A, Chae SS, Cowan AE, Han DK, Proia RL, Hla T (2004) Sphingosine 1-phosphate receptor regulation of N-cadherin mediates vascular stabilization. Genes Dev 18(19):2392–2403PubMedCrossRefGoogle Scholar
  56. Parizi M, Howard EW, Tomasek JJ (2000) Regulation of LPA-promoted myofibroblast contraction: role of Rho, myosin light chain kinase, and myosin light chain phosphatase. Exp Cell Res 254(2):210–220PubMedCrossRefGoogle Scholar
  57. 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):1245–1251PubMedCrossRefGoogle Scholar
  58. Quadri SK, Bhattacharya J (2007) Resealing of endothelial junctions by focal adhesion kinase. Am J Physiol Lung Cell Mol Physiol 292(1):L334–L342PubMedCrossRefGoogle Scholar
  59. Quadri SK, Bhattacharjee M, Parthasarathi K, Tanita T, Bhattacharya J (2003) Endothelial barrier strengthening by activation of focal adhesion kinase. J Biol Chem 278(15):13342–13349PubMedCrossRefGoogle Scholar
  60. Rogers DF, Boschetto P, Barnes PJ (1989) Plasma exudation. Correlation between Evans blue dye and radiolabeled albumin in guinea pig airways in vivo. J Pharmacol Methods 21(4):309–315PubMedCrossRefGoogle Scholar
  61. Rosen H, Goetzl EJ (2005) Sphingosine 1-phosphate and its receptors: an autocrine and paracrine network. Nat Rev Immunol 5(7):560–570PubMedCrossRefGoogle Scholar
  62. Rosen H, Sanna MG, Cahalan SM, Gonzalez-Cabrera PJ (2007) Tipping the gatekeeper: S1P regulation of endothelial barrier function. Trends Immunol 28(3):102–107PubMedCrossRefGoogle Scholar
  63. Rosenfeldt HM, Hobson JP, Maceyka M, Olivera A, Nava VE, Milstien S, Spiegel S (2001) EDG-1 links the PDGF receptor to Src and focal adhesion kinase activation leading to lamellipodia formation and cell migration. FASEB J 15(14):2649–2659PubMedCrossRefGoogle Scholar
  64. Rosenfeldt HM, Amrani Y, Watterson KR, Murthy KS, Panettieri RA Jr, Spiegel S (2003) Sphingosine 1-phosphate stimulates contraction of human airway smooth muscle cells. FASEB J 17(13):1789–1799PubMedCrossRefGoogle Scholar
  65. Ryu Y, Takuwa N, Sugimoto N, Sakurada S, Usui S, Okamoto H, Matsui O, Takuwa Y (2002) Sphingosine-1-phosphate, a platelet-derived lysophospholipid mediator, negatively regulates cellular Rac activity and cell migration in vascular smooth muscle cells. Circ Res 90(3): 325–332PubMedCrossRefGoogle Scholar
  66. Saba JD, Hla T (2004) Point-counterpoint of sphingosine 1-phosphate metabolism. Circ Res 94(6): 724–734PubMedCrossRefGoogle Scholar
  67. 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):394–402PubMedCrossRefGoogle Scholar
  68. Sanna MG, Wang SK, Gonzalez-Cabrera PJ, Don A, Marsolais D, Matheu MP, Wei SH, Parker I, Jo E, Cheng WC, Cahalan MD, Wong CH, Rosen H (2006) Enhancement of capillary leakage and restoration of lymphocyte egress by a chiral S1P1 antagonist in vivo. Nat Chem Biol 2(8): 434–441PubMedCrossRefGoogle Scholar
  69. Schuchardt M, Tölle M, Prüfer J, van der Giet M (2011) Pharmacological relevance and potential of sphingosine 1-phosphate in the vascular system. Br J Pharmacol 163(6):1140–1162. doi: 10.1111/j.1476-5381.2011.01260.x PubMedCrossRefGoogle Scholar
  70. 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):662–673PubMedCrossRefGoogle Scholar
  71. Shikata Y, Birukov KG, Birukova AA, Verin A, Garcia JG (2003a) Involvement of site-specific FAK phosphorylation in sphingosine-1 phosphate- and thrombin-induced focal adhesion remodeling: role of Src and GIT. FASEB J 17(15):2240–2249PubMedCrossRefGoogle Scholar
  72. Shikata Y, Birukov KG, Garcia JG (2003b) S1P induces FA remodeling in human pulmonary endothelial cells: role of Rac, GIT1, FAK, and paxillin. J Appl Physiol 94(3):1193–1203PubMedGoogle Scholar
  73. Singleton PA, Dudek SM, Chiang ET, Garcia JG (2005) Regulation of sphingosine 1-phosphate-induced endothelial cytoskeletal rearrangement and barrier enhancement by S1P1 receptor, PI3 kinase, Tiam1/Rac1, and alpha-actinin. FASEB J 19(12):1646–1656PubMedCrossRefGoogle Scholar
  74. Singleton PA, Lingen MW, Fekete MJ, Garcia JG, Moss J (2006) Methylnaltrexone inhibits opiate and VEGF-induced angiogenesis: role of receptor transactivation. Microvasc Res 72(1–2):3–11PubMedCrossRefGoogle Scholar
  75. Singleton PA, Moreno-Vinasco L, Sammani S, Wanderling SL, Moss J, Garcia JG (2007) Attenuation of vascular permeability by methylnaltrexone: role of mOP-R and S1P3 transactivation. Am J Respir Cell Mol Biol 37(2):222–231PubMedCrossRefGoogle Scholar
  76. Snider AJ, Orr Gandy KA, Obeid LM (2010) Sphingosine kinase: role in regulation of bioactive sphingolipid mediators in inflammation. Biochimie 92(6):707–715PubMedCrossRefGoogle Scholar
  77. Spiegel S, Milstien S (2003) Sphingosine-1-phosphate: an enigmatic signalling lipid. Nat Rev Mol Cell Biol 4(5):397–407PubMedCrossRefGoogle Scholar
  78. Sun X, Shikata Y, Wang L, Ohmori K, Watanabe N, Wada J, Shikata K, Birukov KG, Makino H, Jacobson JR, Dudek SM, Garcia JG (2009) Enhanced interaction between focal adhesion and adherens junction proteins: involvement in sphingosine 1-phosphate-induced endothelial barrier enhancement. Microvasc Res 77(3):304–313PubMedCrossRefGoogle Scholar
  79. Tani M, Ito M, Igarashi Y (2007) Ceramide/sphingosine/sphingosine 1-phosphate metabolism on the cell surface and in the extracellular space. Review. Cell Signal 19(2):229–237PubMedCrossRefGoogle Scholar
  80. 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):461–471PubMedCrossRefGoogle Scholar
  81. 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–C821PubMedGoogle Scholar
  82. Vestweber D (2008) VE-cadherin: the major endothelial adhesion molecule controlling cellular junctions and blood vessel formation. Review. Arterioscler Thromb Vasc Biol 28(2):223–232PubMedCrossRefGoogle Scholar
  83. Vestweber D, Winderlich M, Cagna G, Nottebaum AF (2009) Cell adhesion dynamics at endothelial junctions: VE-cadherin as a major player. Trends Cell Biol 19(1):8–15PubMedCrossRefGoogle Scholar
  84. Vouret-Craviari V, Bourcier C, Boulter E, van Obberghen-Schilling E (2002) Distinct signals via Rho GTPases and Src drive shape changes by thrombin and sphingosine-1-phosphate in endothelial cells. J Cell Sci 115(Pt 12):2475–2484PubMedGoogle Scholar
  85. Waeber C, Blondeau N, Salomone S (2004) Vascular sphingosine-1-phosphate S1P1 and S1P3 receptors. Review. Drug News Perspect 17(6):365–382PubMedCrossRefGoogle Scholar
  86. Wang L, Dudek SM (2009) Regulation of vascular permeability by sphingosine 1-phosphate. Microvasc Res 77(1):39–45PubMedCrossRefGoogle Scholar
  87. Wang Y, Zheng XR, Riddick N, Bryden M, Baur W, Zhang X, Surks HK (2009) ROCK isoform regulation of myosin phosphatase and contractility in vascular smooth muscle cells. Circ Res 104(4):531–540PubMedCrossRefGoogle Scholar
  88. Waterman-Storer CM, Worthylake RA, Liu BP, Burridge K, Salmon ED (1999) Microtubule growth activates Rac1 to promote lamellipodial protrusion in fibroblasts. Nat Cell Biol 1(1): 45–50PubMedCrossRefGoogle Scholar
  89. Wojciak-Stothard B, Tsang LY, Paleolog E, Hall SM, Haworth SG (2006) Rac1 and RhoA as regulators of endothelial phenotype and barrier function in hypoxia-induced neonatal pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 290(6):L1173–L1182PubMedCrossRefGoogle Scholar
  90. Worthylake RA, Lemoine S, Watson JM, Burridge K (2001) RhoA is required for monocyte tail retraction during transendothelial migration. J Cell Biol 154(1):147–160PubMedCrossRefGoogle Scholar
  91. Wu MH (2005) Endothelial focal adhesions and barrier function. Review. J Physiol 569(Pt 2): 359–366PubMedCrossRefGoogle Scholar
  92. Wysolmerski RB, Lagunoff D (1990) Involvement of myosin light-chain kinase in endothelial cell retraction. Proc Natl Acad Sci USA 87(1):16–20PubMedCrossRefGoogle Scholar
  93. 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–C1318PubMedCrossRefGoogle Scholar
  94. Yang L, Yatomi Y, Miura Y, Satoh K, Ozaki Y (1999) Metabolism and functional effects of sphingolipids in blood cells. Br J Haematol 107(2):282–293PubMedCrossRefGoogle Scholar
  95. Yatomi Y, Ruan F, Hakomori S, Igarashi Y (1995) Sphingosine-1-phosphate: a platelet-activating sphingolipid released from agonist-stimulated human platelets. Blood 86(1):193–202PubMedGoogle Scholar
  96. Yuan CS, Doshan H, Charney MR, O’connor M, Karrison T, Maleckar SA, Israel RJ, Moss J (2005) Tolerability, gut effects, and pharmacokinetics of methylnaltrexone following repeated intravenous administration in humans. J Clin Pharmacol 45(5):538–546PubMedCrossRefGoogle Scholar
  97. Zhang Q, Magnusson MK, Mosher DF (1997) Lysophosphatidic acid and microtubule-destabilizing agents stimulate fibronectin matrix assembly through Rho-dependent actin stress fiber formation and cell contraction. Mol Biol Cell 8(8):1415–1425PubMedGoogle Scholar
  98. Zhao Y, Kalari SK, Usatyuk PV, Gorshkova I, He D, Watkins T, Brindley DN, Sun C, Bittman R, Garcia JG, Berdyshev EV, Natarajan V (2007) Intracellular generation of sphingosine 1-phosphate in human lung endothelial cells: role of lipid phosphate phosphatase-1 and sphingosine kinase 1. J Biol Chem 282(19):14165–14177PubMedCrossRefGoogle Scholar
  99. Zondag GC, Postma FR, Etten IV, Verlaan I, Moolenaar WH (1998) Sphingosine 1-phosphate signalling through the G-protein-coupled receptor Edg-1. Biochem J 330(Pt 2):605–609PubMedGoogle Scholar

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© Springer-Verlag Wien 2013

Authors and Affiliations

  1. 1.Department of Medicine, Institute for Personalized Respiratory MedicineThe University of Illinois at ChicagoChicagoUSA
  2. 2.Pharmacology & BioengineeringChicagoUSA

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