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The role of sphingolipids in endothelial barrier function

  • Peter L. Jernigan

    From left to right: Peter L. Jernigan and Richard S. Hoehn are surgical residents at the University of Cincinnati College of Medicine currently participating in a research fellowship. Their areas of research interest include blood banking, trauma, and sphingolipid biology. Amy T. Makley and Timothy A. Pritts are trauma surgeons at the University of Cincinnati with research interests including blood banking, hemorrhagic shock and resuscitation, and lung injury. Michael J. Edwards is a surgical oncologist and the chairman of surgery at the University of Cincinnati with specific research interests including sphingolipids and translational medicine.

    , Amy T. Makley , Richard S. Hoehn , Michael J. Edwards and Timothy A. Pritts EMAIL logo
Published/Copyright: May 1, 2015

Abstract

Sphingolipids are a ubiquitous family of essential lipids with an increasingly understood role as biologically active mediators in numerous physiologic and pathologic processes. Two particular sphingolipid species, sphingosine-1-phosphate and ceramide, and their metabolites interact both directly and indirectly with endothelial cells to regulate vascular permeability. Sphingosine-1-phosphate generally augments endothelial integrity while ceramide tends to promote vascular leak, and a tight balance between the two is necessary to maintain normal physiologic function. The mechanisms by which sphingolipids regulate endothelial barrier function are complex and occur through multiple different pathways, and disruptions or imbalances in these pathways have been implicated in a number of specific disease processes. With improved understanding of sphingolipid biology, endothelial function, and the interactions between the two, several targets for therapeutic intervention have emerged and there is immense potential for further advancement in this field.


Corresponding author: Timothy A. Pritts, Department of Surgery and Institute for Military Medicine, University of Cincinnati, 231 Albert Sabin Way, Mail Location 0558, Cincinnati, OH 45267-0558, USA, e-mail:

About the author

Peter L. Jernigan

From left to right: Peter L. Jernigan and Richard S. Hoehn are surgical residents at the University of Cincinnati College of Medicine currently participating in a research fellowship. Their areas of research interest include blood banking, trauma, and sphingolipid biology. Amy T. Makley and Timothy A. Pritts are trauma surgeons at the University of Cincinnati with research interests including blood banking, hemorrhagic shock and resuscitation, and lung injury. Michael J. Edwards is a surgical oncologist and the chairman of surgery at the University of Cincinnati with specific research interests including sphingolipids and translational medicine.

References

Adyshev, D.M., Moldobaeva, N.K., Elangovan, V.R., Garcia, J.G., and Dudek, S.M. (2011). Differential involvement of ezrin/radixin/moesin proteins in sphingosine 1-phosphate-induced human pulmonary endothelial cell barrier enhancement. Cell. Signal. 23, 2086–2096.10.1016/j.cellsig.2011.08.003Search in Google Scholar PubMed PubMed Central

Allende, M.L., Yamashita, T., and Proia R.L. (2003). G-protein-coupled receptor S1P1 acts within endothelial cells to regulate vascular maturation. Blood 102, 3665–3667.10.1182/blood-2003-02-0460Search in Google Scholar PubMed

Barlage, S., Gnewuch, C., Liebisch, G., Wolf, Z., Audebert, F.X., Gluck, T., Frohlich, D., Kramer, B.K., Rothe, G., and Schmitz, G. (2009). Changes in HDL-associated apolipoproteins relate to mortality in human sepsis and correlate to monocyte and platelet activation. Intensive Care Med. 35, 1877–1885.10.1007/s00134-009-1609-ySearch in Google Scholar PubMed

Bazzoni, G. and Dejana, E. (2004). Endothelial cell-to-cell junctions – molecular organization and role in vascular homeostasis. Physiol. Rev. 84, 869–901.10.1152/physrev.00035.2003Search in Google Scholar PubMed

Beckmann, N., Sharma, D., Gulbins, E., Becker, K.A., and Edelmann, B. (2014). Inhibition of acid sphingomyelinase by tricyclic antidepressants and analogons. Front. Physiol. 5, 331.10.3389/fphys.2014.00331Search in Google Scholar PubMed PubMed Central

Belvitch, P. and Dudek, S.M. (2012). Role of FAK in S1P-regulated endothelial permeability. Microvasc. Res. 83, 22–30.10.1016/j.mvr.2011.08.012Search in Google Scholar PubMed PubMed Central

Bonnaud, S., Niaudet, C., Legoux, F., Corre, I., Delpon, G., Saulquin, X., Fuks, Z., Gaugler, M.H., Kolesnick, R., and Paris, F. (2010). Sphingosine-1-phosphate activates the AKT pathway to protect small intestines from radiation-induced endothelial apoptosis. Cancer Res. 70, 9905–9915.10.1158/0008-5472.CAN-10-2043Search in Google Scholar PubMed

Bradley, E., Dasgupta, S., Jiang, X., Zhao, X., Zhu, G., He, Q., Dinkins, M., Bieberich, E., and Wang, G. (2014). Critical role of Spns2, a sphingosine-1-phosphate transporter, in lung cancer cell survival and migration. PLoS One 9, e110119.10.1371/journal.pone.0110119Search in Google Scholar PubMed PubMed Central

Camerer, E., Regard, J.B., Cornelissen, I., Srinivasan, Y., Duong, D.N., Palmer, D., Pham, T.H., Wong, J.S., Pappu, R., and Coughlin, S.R. (2009). Sphingosine-1-phosphate in the plasma compartment regulates basal and inflammation-induced vascular leak in mice. J. Clin. Invest. 119, 1871–1879.10.1172/JCI38575Search in Google Scholar

Cines, D.B., Pollak, E.S., Buck, C.A., Loscalzo, J., Zimmerman, G.A., McEver, R.P., Pober, J.S., Wick, T.M., Konkle, B.A., Schwartz, B.S., et al. (1998). Endothelial cells in physiology and in the pathophysiology of vascular disorders. Blood 91, 3527–3561.Search in Google Scholar

Claus, R.A., Bunck, A.C., Bockmeyer, C.L., Brunkhorst, F.M., Losche, W., Kinscherf, R., and Deigner, H.P. (2005). Role of increased sphingomyelinase activity in apoptosis and organ failure of patients with severe sepsis. FASEB J. 19, 1719–1721.10.1096/fj.04-2842fjeSearch in Google Scholar PubMed

Corada, M., Mariotti, M., Thurston, G., Smith, K., Kunkel, R., Brockhaus, M., Lampugnani, M.G., Martin-Padura, I., Stoppacciaro, A., Ruco, L., et al. (1999). Vascular endothelial-cadherin is an important determinant of microvascular integrity in vivo. Proc. Natl. Acad. Sci. USA 96, 9815–9820.10.1073/pnas.96.17.9815Search in Google Scholar PubMed PubMed Central

Czarny, M. and Schnitzer, J.E. (2004). Neutral sphingomyelinase inhibitor scyphostatin prevents and ceramide mimics mechanotransduction in vascular endothelium. Am. J. Physiol. Heart Circ. Physiol. 287, H1344–H1352.10.1152/ajpheart.00222.2004Search in Google Scholar PubMed

Dejana, E. (2004). Endothelial cell-cell junctions: happy together. Nat. Rev. Mol. Cell. Biol. 5, 261–270.10.1038/nrm1357Search in Google Scholar PubMed

Dejana, E., Bazzoni, G., and Lampugnani, M.G. (1999). Vascular endothelial (VE)-cadherin: only an intercellular glue? Exp. Cell Res. 252, 13–19.10.1006/excr.1999.4601Search in Google Scholar PubMed

Delogu, G., Famularo, G., Amati, F., Signore, L., Antonucci, A., Trinchieri, V., Di Marzio, L., and Cifone, M.G. (1999). Ceramide concentrations in septic patients: a possible marker of multiple organ dysfunction syndrome. Crit. Care Med. 27, 2413–2417.10.1097/00003246-199911000-00015Search in Google Scholar PubMed

Drobnik, W., Liebisch, G., Audebert, F.X., Frohlich, D., Gluck, T., Vogel, P., Rothe, G., and Schmitz, G. (2003). Plasma ceramide and lysophosphatidylcholine inversely correlate with mortality in sepsis patients. J. Lipid Res. 44, 754–761.10.1194/jlr.M200401-JLR200Search in Google Scholar PubMed

Dudek, S.M. and Garcia, J.G. (2001). Cytoskeletal regulation of pulmonary vascular permeability. J. Appl. Physiol. 91, 1487–1500.10.1152/jappl.2001.91.4.1487Search in Google Scholar PubMed

Finigan, J.H., Dudek, S.M., Singleton, P.A., Chiang, E.T., Jacobson, J.R., Camp, S.M., Ye, S.Q., and Garcia, J.G. (2005). Activated protein C mediates novel lung endothelial barrier enhancement: role of sphingosine 1-phosphate receptor transactivation. J. Biol. Chem. 280, 17286–17293.10.1074/jbc.M412427200Search in Google Scholar PubMed

Furuse, M. and Tsukita, S. (2006). Claudins in occluding junctions of humans and flies. Trends Cell Biol. 16, 181–188.10.1016/j.tcb.2006.02.006Search in Google Scholar PubMed

Futerman, A.H. and van Meer, G. (2004). The cell biology of lysosomal storage disorders. Nat. Rev. Mol. Cell. Biol. 5, 554–565.10.1038/nrm1423Search in Google Scholar PubMed

Gao, X., Kouklis, P., Xu, N., Minshall, R.D., Sandoval, R., Vogel S.M., and Malik, A.B. (2000). Reversibility of increased microvessel permeability in response to VE-cadherin disassembly. Am. J. Physiol. Lung Cell. Mol. Physiol. 279, L1218–1225.10.1152/ajplung.2000.279.6.L1218Search in Google Scholar

Garcia, J.G., Liu, F., Verin, A.D., Birukova, A., Dechert, M.A., Gerthoffer, W.T., Bamberg, J.R., and English, D. (2001). Sphingosine 1-phosphate promotes endothelial cell barrier integrity by Edg-dependent cytoskeletal rearrangement. J. Clin. Invest. 108, 689–701.10.1172/JCI12450Search in Google Scholar

Gault, C.R., Obeid, L.M., and Hannun, Y.A. (2010). An overview of sphingolipid metabolism: from synthesis to breakdown. Adv. Exp. Med. Biol. 688, 1–23.10.1007/978-1-4419-6741-1_1Search in Google Scholar

Gavard, J. and Gutkind, J.S. (2006). VEGF controls endothelial-cell permeability by promoting the β-arrestin-dependent endocytosis of VE-cadherin. Nat. Cell Biol. 8, 1223–1234.10.1038/ncb1486Search in Google Scholar

Goggel, R., Winoto-Morbach, S., Vielhaber, G., Imai, Y., Lindner, K., Brade, L., Brade, H., Ehlers, S., Slutsky, A.S., Schutze, S., et al. (2004). PAF-mediated pulmonary edema: a new role for acid sphingomyelinase and ceramide. Nat. Med. 10, 155–160.10.1038/nm977Search in Google Scholar

Gulbins, E. (2003). Regulation of death receptor signaling and apoptosis by ceramide. Pharmacol. Res. 47, 393–399.10.1016/S1043-6618(03)00052-5Search in Google Scholar

Gumbiner, B.M. (2005). Regulation of cadherin-mediated adhesion in morphogenesis. Nat. Rev. Mol. Cell. Biol. 6, 622–634.10.1038/nrm1699Search in Google Scholar PubMed

Gupta, N., Nodzenski, E., Khodarev, N.N., Yu, J., Khorasani, L., Beckett, M.A., Kufe, D.W., and Weichselbaum, R.R. (2001). Angiostatin effects on endothelial cells mediated by ceramide and RhoA. EMBO Rep. 2, 536–540.10.1093/embo-reports/kve115Search in Google Scholar PubMed PubMed Central

Haimovitz-Friedman, A., Cordon-Cardo, C., Bayoumy, S., Garzotto, M., McLoughlin, M., Gallily, R., Edwards, C.K., 3rd, Schuchman, E.H., Fuks, Z., and Kolesnick, R. (1997a). Lipopolysaccharide induces disseminated endothelial apoptosis requiring ceramide generation. J. Exp. Med. 186, 1831–1841.10.1084/jem.186.11.1831Search in Google Scholar PubMed PubMed Central

Haimovitz-Friedman, A., Kolesnick, R.N., and Fuks, Z. (1997b). Ceramide signaling in apoptosis. Br. Med. Bull. 53, 539–553.10.1093/oxfordjournals.bmb.a011629Search in Google Scholar PubMed

Halmer, R., Walter, S., and Fassbender, K. (2014). Sphingolipids: important players in multiple sclerosis. Cell. Physiol. Biochem. 34, 111–118.10.1159/000362988Search in Google Scholar

Hannun, Y.A. and Obeid, L.M. (2002). The ceramide-centric universe of lipid-mediated cell regulation: stress encounters of the lipid kind. J. Biol. Chem. 277, 25847–25850.10.1074/jbc.R200008200Search in Google Scholar

Hannun, Y.A. and Obeid, L.M. (2008). Principles of bioactive lipid signalling: lessons from sphingolipids. Nat. Rev. Mol. Cell. Biol. 9, 139–150.10.1038/nrm2329Search in Google Scholar

Henry, B., Ziobro, R., Becker, K.A., Kolesnick, R., and Gulbins, E. (2013). Acid sphingomyelinase. In: Handbook of Experimental Pharmacology, Vol. 215, Part II, E. Gulbins and I. Petrache, eds. (Vienna, Austria: Springer Vienna), pp. 77–88.10.1007/978-3-7091-1368-4_4Search in Google Scholar

Hisano, Y., Kobayashi, N., Yamaguchi, A., and Nishi, T. (2012). Mouse SPNS2 functions as a sphingosine-1- phosphate transporter in vascular endothelial cells. PLoS One 7, e38941.10.1371/journal.pone.0038941Search in Google Scholar

Hla, T. and Brinkmann, V. (2011). Sphingosine 1-phosphate (S1P): physiology and the effects of S1P receptor modulation. Neurology 76 (8 Suppl 3), S3–S8.10.1212/WNL.0b013e31820d5ec1Search in Google Scholar

Horiuchi, M. and Mogi, M. (2011). Role of angiotensin II receptor subtype activation in cognitive function and ischaemic brain damage. Br. J. Pharmacol. 163, 1122–1130.10.1111/j.1476-5381.2010.01167.xSearch in Google Scholar

Igarashi, J., Thatte, H.S., Prabhakar, P., Golan, D.E., and Michel, T. (1999). Calcium-independent activation of endothelial nitric oxide synthase by ceramide. Proc. Natl. Acad. Sci. USA 96, 12583–12588.10.1073/pnas.96.22.12583Search in Google Scholar

Jmoudiak, M. and Futerman, A.H. (2005). Gaucher disease: pathological mechanisms and modern management. Br. J. Haematol. 129, 178–188.10.1111/j.1365-2141.2004.05351.xSearch in Google Scholar

Kolesnick, R. and Golde, D.W. (1994). The sphingomyelin pathway in tumor necrosis factor and interleukin-1 signaling. Cell 77, 325–328.10.1016/0092-8674(94)90147-3Search in Google Scholar

Kolliputi, N., Galam, L., Parthasarathy, P.T., Tipparaju, S.M., and Lockey, R.F. (2012). NALP-3 inflammasome silencing attenuates ceramide-induced transepithelial permeability. J. Cell. Physiol. 227, 3310–3316.10.1002/jcp.24026Search in Google Scholar PubMed PubMed Central

Kono, M., Mi, Y., Liu, Y., Sasaki, T., Allende, M.L., Wu, Y.P., Yamashita, T., and Proia, R.L. (2004). The sphingosine-1-phosphate receptors S1P1, S1P2, and S1P3 function coordinately during embryonic angiogenesis. J. Biol. Chem. 279, 29367–29373.10.1074/jbc.M403937200Search in Google Scholar PubMed

Kuebler, W.M., Yang, Y., Samapati, R., and Uhlig, S. (2010). Vascular barrier regulation by PAF, ceramide, caveolae, and NO – an intricate signaling network with discrepant effects in the pulmonary and systemic vasculature. Cell. Physiol. Biochem. 26, 29–40.10.1159/000315103Search in Google Scholar PubMed

Kumaraswamy, S.B., Linder, A., Akesson, P., and Dahlback, B. (2012). Decreased plasma concentrations of apolipoprotein M in sepsis and systemic inflammatory response syndromes. Crit. Care 16, R60.10.1186/cc11305Search in Google Scholar PubMed PubMed Central

Lee, J.F., Zeng, Q., Ozaki, H., Wang, L., Hand, A.R., Hla, T., Wang, E., and Lee, M.J. (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, 29190–29200.10.1074/jbc.M604310200Search in Google Scholar PubMed

Li, Q., Chen, B., Zeng, C., Fan, A., Yuan, Y., Guo, X., Huang, X., and Huang, Q. (2015). Differential activation of receptors and signal pathways upon stimulation by different doses of sphingosine-1-phosphate in endothelial cells. Exp. Physiol. 100, 95–107.10.1113/expphysiol.2014.082149Search in Google Scholar PubMed

Lin, X., Fuks, Z., and Kolesnick, R. (2000). Ceramide mediates radiation-induced death of endothelium. Crit. Care Med. 28 (4 Suppl), N87–N93.10.1097/00003246-200004001-00010Search in Google Scholar PubMed

Lindner, K., Uhlig, U., and Uhlig, S. (2005). Ceramide alters endothelial cell permeability by a non-apoptotic mechanism. Br. J. Pharmacol. 145, 132–140.10.1038/sj.bjp.0706173Search in Google Scholar PubMed PubMed Central

Linn, S.C., Kim, H.S., Keane, E.M., Andras, L.M., Wang, E., and Merrill, A.H., Jr. (2001). Regulation of de novo sphingolipid biosynthesis and the toxic consequences of its disruption. Biochem. Soc. Trans. 29, 831–835.10.1042/bst0290831Search in Google Scholar

Liu, H.B., Cui, N.Q., Wang, Q., Li, D.H., and Xue, X.P. (2008). Sphingosine-1-phosphate and its analogue FTY720 diminish acute pulmonary injury in rats with acute necrotizing pancreatitis. Pancreas 36, e10–e15.10.1097/MPA.0b013e31815f3905Search in Google Scholar PubMed

Lucke, S. and Levkau, B. (2010). Endothelial functions of sphingosine-1-phosphate. Cell Physiol. Biochem. 26, 87–96.10.1159/000315109Search in Google Scholar PubMed

Maceyka, M. and Spiegel, S. (2014). Sphingolipid metabolites in inflammatory disease. Nature 510, 58–67.10.1038/nature13475Search in Google Scholar PubMed PubMed Central

MacKichan, M.L. and DeFranco, A.L. (1999). Role of ceramide in lipopolysaccharide (LPS)-induced signaling. LPS increases ceramide rather than acting as a structural homolog. J. Biol. Chem. 274, 1767–1775.10.1074/jbc.274.3.1767Search in Google Scholar PubMed

Majno, G., Shea, S.M., and Leventhal, M. (1969). Endothelial contraction induced by histamine-type mediators: an electron microscopic study. J. Cell. Biol. 42, 647–672.10.1083/jcb.42.3.647Search in Google Scholar PubMed PubMed Central

Marathe, S., Schissel, S.L., Yellin, M.J., Beatini, N., Mintzer, R., Williams, K.J., and Tabas, I. (1998). Human vascular endothelial cells are a rich and regulatable source of secretory sphingomyelinase. Implications for early atherogenesis and ceramide-mediated cell signaling. J. Biol. Chem. 273, 4081–4088.10.1074/jbc.273.7.4081Search in Google Scholar PubMed

Mathias, S., Pena, L.A., and Kolesnick, R. (1998). Signal transduction of stress via ceramide. Biochem. J. 335, 465–480.10.1042/bj3350465Search in Google Scholar PubMed PubMed Central

McVerry, B.J., Peng, X., Hassoun, P.M., Sammani, S., Simon, B.A., and Garcia, J.G. (2004). Sphingosine 1-phosphate reduces vascular leak in murine and canine models of acute lung injury. Am. J. Respir. Crit. Care Med. 170, 987–993.10.1164/rccm.200405-684OCSearch in Google Scholar PubMed

Mehta, D. and Malik, A.B. (2006). Signaling mechanisms regulating endothelial permeability. Physiol. Rev. 86, 279–367.10.1152/physrev.00012.2005Search in Google Scholar PubMed

Mehta, D., Ravindran, K., and Kuebler, W.M. (2014). Perspective: novel regulators of endothelial barrier function. Am. J. Physiol. Lung Cell. Mol. Physiol. 307, L924–L935.Search in Google Scholar

Morel, N.M., Petruzzo, P.P., Hechtman, H.B., and Shepro, D. (1990). Inflammatory agonists that increase microvascular permeability in vivo stimulate cultured pulmonary microvessel endothelial cell contraction. Inflammation 14, 571–583.10.1007/BF00914277Search in Google Scholar PubMed

Nishi, T., Kobayashi, N., Hisano, Y., Kawahara, A., and Yamaguchi, A. (2014). Molecular and physiological functions of sphingosine 1-phosphate transporters. Biochim. Biophys. Acta 1841, 759–765.10.1016/j.bbalip.2013.07.012Search in Google Scholar PubMed

Obinata, H. and Hla, T. (2012). Sphingosine 1-phosphate in coagulation and inflammation. Semin. Immunopathol. 34, 73–91.10.1007/s00281-011-0287-3Search in Google Scholar

Pappu, R., Schwab, S.R., Cornelissen, I., Pereira, J.P., Regard, J.B., Xu, Y., Camerer, E., Zheng, Y.W., Huang, Y., Cyster, J.G., et al. (2007). Promotion of lymphocyte egress into blood and lymph by distinct sources of sphingosine-1-phosphate. Science 316, 295–298.10.1126/science.1139221Search in Google Scholar

Peng, X., Hassoun, P.M., Sammani, S., McVerry, B.J., Burne, M.J., Rabb, H., Pearse, D., Tuder, R.M., and Garcia, J.G. (2004). Protective effects of sphingosine 1-phosphate in murine endotoxin-induced inflammatory lung injury. Am. J. Respir. Crit. Care Med. 169, 1245–1251.10.1164/rccm.200309-1258OCSearch in Google Scholar

Petrache, I., Natarajan, V., Zhen, L., Medler, T.R., Richter, A.T., Cho, C., Hubbard, W.C., Berdyshev, E.V., and Tuder, R.M. (2005). Ceramide upregulation causes pulmonary cell apoptosis and emphysema-like disease in mice. Nat. Med. 11, 491–498.10.1038/nm1238Search in Google Scholar

Petrache, I., Petrusca, D.N., Bowler, R.P., and Kamocki, K. (2011). Involvement of ceramide in cell death responses in the pulmonary circulation. Proc. Am. Thorac. Soc. 8, 492–496.10.1513/pats.201104-034MWSearch in Google Scholar

Pfeiffer, A., Bottcher, A., Orso, E., Kapinsky, M., Nagy, P., Bodnar, A., Spreitzer, I., Liebisch, G., Drobnik, W., Gempel, K., et al. (2001). Lipopolysaccharide and ceramide docking to CD14 provokes ligand-specific receptor clustering in rafts. Eur. J. Immunol. 31, 3153–3164.10.1002/1521-4141(200111)31:11<3153::AID-IMMU3153>3.0.CO;2-0Search in Google Scholar

Predescu, D. and Palade, G.E. (1993). Plasmalemmal vesicles represent the large pore system of continuous microvascular endothelium. Am. J. Physiol. 265, H725–H733.10.1152/ajpheart.1993.265.2.H725Search in Google Scholar

Pries, A.R. and Kuebler, W.M. (2006). Normal endothelium. Handb. Exp. Pharmacol. 176, 1–40.10.1007/3-540-32967-6_1Search in Google Scholar

Qiao, R.L., Wang, H.S., Yan, W., Odekon, L.E., Del Vecchio, P.J., Smith, T.J., and Malik, A.B. (1995). Extracellular matrix hyaluronan is a determinant of the endothelial barrier. Am. J. Physiol. 269, C103–C109.10.1152/ajpcell.1995.269.1.C103Search in Google Scholar

Rigor, R.R., Shen, Q., Pivetti, C.D., Wu, M.H., and Yuan, S.Y. (2013). Myosin light chain kinase signaling in endothelial barrier dysfunction. Med. Res. Rev. 33, 911–933.10.1002/med.21270Search in Google Scholar

Ruffer, C., Strey, A., Janning, A., Kim, K.S., and Gerke, V. (2004). Cell-cell junctions of dermal microvascular endothelial cells contain tight and adherens junction proteins in spatial proximity. Biochemistry 43, 5360–5369.10.1021/bi035517cSearch in Google Scholar PubMed

Samapati, R., Yang, Y., Yin, J., Stoerger, C., Arenz, C., Dietrich, A., Gudermann, T., Adam, D., Wu, S., Freichel, M., et al. (2012). Lung endothelial Ca2+ and permeability response to platelet-activating factor is mediated by acid sphingomyelinase and transient receptor potential classical 6. Am. J. Respir. Crit. Care Med. 185, 160–170.10.1164/rccm.201104-0717OCSearch in Google Scholar PubMed

Sammani, S., Moreno-Vinasco, L., Mirzapoiazova, T., Singleton, P.A., Chiang, E.T., Evenoski, C.L., Wang, T., Mathew, B., Husain, A., Moitra, J., et al. (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, 394–402.10.1165/rcmb.2009-0223OCSearch in Google Scholar PubMed PubMed Central

Sanchez, T., Skoura, A., Wu, M.T., Casserly, B., Harrington, E.O., and 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, 1312–1318.10.1161/ATVBAHA.107.143735Search in Google Scholar PubMed

Schaphorst, K.L., Chiang, E., Jacobs, K.N., Zaiman, A., Natarajan, V., Wigley, F., and Garcia, J.G. (2003). Role of sphingosine-1 phosphate in the enhancement of endothelial barrier integrity by platelet-released products. Am. J. Physiol. Cell. Mol. Physiol. 285, L258–L267.10.1152/ajplung.00311.2002Search in Google Scholar PubMed

Schuchardt, M., Tolle, M., Prufer, J., and van der Giet, M. (2011). Pharmacological relevance and potential of sphingosine 1-phosphate in the vascular system. Br. J. Pharmacol. 163, 1140–1162.10.1111/j.1476-5381.2011.01260.xSearch in Google Scholar PubMed PubMed Central

Schwab, S.R., Pereira, J.P., Matloubian, M., Xu, Y., Huang, Y., and Cyster, J.G. (2005). Lymphocyte sequestration through S1P lyase inhibition and disruption of S1P gradients. Science 309, 1735–1739.10.1126/science.1113640Search in Google Scholar PubMed

Schweitzer, K.S., Hatoum, H., Brown, M.B., Gupta, M., Justice, M.J., Beteck, B., Van Demark, M., Gu, Y., Presson, R.G., Jr., Hubbard, W.C., et al. (2011). Mechanisms of lung endothelial barrier disruption induced by cigarette smoke: role of oxidative stress and ceramides. Am. J. Physiol. Lung Cell. Mol. Physiol. 301, L836–846.10.1152/ajplung.00385.2010Search in Google Scholar PubMed PubMed Central

Singleton, P.A., Dudek, S.M., Chiang, E.T., and Garcia, J.G. (2005). Regulation of sphingosine 1-phosphate-induced endothelial cytoskeletal rearrangement and barrier enhancement by S1P1 receptor, PI3 kinase, Tiam1/Rac1, and a-actinin. FASEB J. 19, 1646–1656.10.1096/fj.05-3928comSearch in Google Scholar PubMed

Skoura, A. and Hla, T. (2009). Regulation of vascular physiology and pathology by the S1P2 receptor subtype. Cardiovasc. Res. 82, 221–228.10.1093/cvr/cvp088Search in Google Scholar PubMed PubMed Central

Spiegel, S. and Milstien, S. (2003). Sphingosine-1-phosphate: an enigmatic signaling lipid. Nat. Rev. Mol. Cell. Biol. 4, 397–407.10.1038/nrm1103Search in Google Scholar PubMed

Spindler, V., Schlegel, N., and Waschke, J. (2010). Role of GTPases in control of microvascular permeability. Cardiovasc. Res. 87, 243–253.10.1093/cvr/cvq086Search in Google Scholar PubMed

Stevens, T., Garcia, J.G., Shasby, D.M., Bhattacharya, J., and Malik, A.B. (2000). Mechanisms regulating endothelial cell barrier function. Am. J. Physiol. Lung Cell. Mol. Physiol. 279, L419–422.10.1152/ajplung.2000.279.3.L419Search in Google Scholar PubMed

Taddei, A., Giampietro, C., Conti, A., Orsenigo, F., Breviario, F., Pirazzoli, V., Potente, M., Daly, C., Dimmeler, S., and Dejana, E. (2008). Endothelial adherens junctions control tight junctions by VE-cadherin-mediated upregulation of claudin-5. Nat. Cell. Biol. 10, 923–934.10.1038/ncb1752Search in Google Scholar PubMed

Takahashi, I., Takahashi, T., Abe, T., Watanabe, W., and Takada, G. (2000). Distribution of acid sphingomyelinase in human various body fluids. Tohoku J. Exp. Med. 192, 61–66.10.1620/tjem.192.61Search in Google Scholar PubMed

Tauseef, M., Kini, V., Knezevic, N., Brannan, M., Ramchandaran, R., Fyrst, H., Saba, J., Vogel, S.M., Malik, A.B., and Mehta, D. (2008). Activation of sphingosine kinase-1 reverses the increase in lung vascular permeability through sphingosine-1-phosphate receptor signaling in endothelial cells. Circ. Res. 103, 1164–1172.10.1161/01.RES.0000338501.84810.51Search in Google Scholar PubMed PubMed Central

Thudichum, J.L.W. (1884). A Treatise on the Chemical Constitution of Brain (London, England: Bailliere, Tindall and Cox).Search in Google Scholar

Tidhar, R. and Futerman, A.H. (2013). The complexity of sphingolipid biosynthesis in the endoplasmic reticulum. Biochim. Biophys. Acta 1833, 2511–2518.10.1016/j.bbamcr.2013.04.010Search in Google Scholar PubMed

Uhlig, S. and Gulbins, E. (2008). Sphingolipids in the lungs. Am. J. Respir. Crit. Care Med. 178, 1100–1114.10.1164/rccm.200804-595SOSearch in Google Scholar PubMed

Uhlig, S., Yang, Y., Waade, J., Wittenberg, C., Babendreyer, A., and Kuebler, W.M. (2014). Differential regulation of lung endothelial permeability in vitro and in situ. Cell. Physiol. Biochem. 34, 1–19.10.1159/000362980Search in Google Scholar PubMed

van Leeuwen, H.J., Heezius, E.C., Dallinga, G.M., van Strijp, J.A., Verhoef, J., and van Kessel, K.P. (2003). Lipoprotein metabolism in patients with severe sepsis. Crit. Care Med. 31, 1359–1366.10.1097/01.CCM.0000059724.08290.51Search in Google Scholar PubMed

Venkataraman, K., Lee, Y.M., Michaud, J., Thangada, S., Ai, Y., Bonkovsky, H.L., Parikh, N.S., Habrukowich, C., and Hla, T. (2008). Vascular endothelium as a contributor of plasma sphingosine 1-phosphate. Circ. Res. 102, 669–676.10.1161/CIRCRESAHA.107.165845Search in Google Scholar PubMed PubMed Central

von Bismarck, P., Klemm, K., Wistädt, C.-F.G., Winoto-Morbach, S., Uhlig, U., Schütze, S., Uhlig, S., Lachmann, B., and Krause, M.F. (2007). Surfactant fortification by topical inhibition of nuclear factor-κB activity in a newborn piglet lavage model. Crit. Care Med. 35, 2309–2318.10.1097/01.CCM.0000281472.47067.45Search in Google Scholar PubMed

von Bismarck, P., Wistadt, C.F., Klemm, K., Winoto-Morbach, S., Uhlig, U., Schutze, S., Adam, D., Lachmann, B., Uhlig, S., and Krause, M.F. (2008). Improved pulmonary function by acid sphingomyelinase inhibition in a newborn piglet lavage model. Am. J. Respir. Crit. Care Med. 177, 1233–1241.10.1164/rccm.200705-752OCSearch in Google Scholar PubMed

Weinbaum, S., Tarbell, J.M., and Damiano, E.R. (2007). The structure and function of the endothelial glycocalyx layer. Annu. Rev. Biomed. Eng. 9, 121–167.10.1146/annurev.bioeng.9.060906.151959Search in Google Scholar PubMed

Wilkerson, B.A. and Argraves, K.M. (2014). The role of sphingosine-1-phosphate in endothelial barrier function. Biochim. Biophys. Acta 1841, 1403–1412.10.1016/j.bbalip.2014.06.012Search in Google Scholar PubMed PubMed Central

Wright, S.D. and Kolesnick, R.N. (1995). Does endotoxin stimulate cells by mimicking ceramide? Immunol. Today 16, 297–302.Search in Google Scholar

Xiong, Y., Yang, P., Proia, R.L., and Hla, T. (2014). Erythrocyte-derived sphingosine 1-phosphate is essential for vascular development. J. Clin. Invest. 124, 4823–4828.10.1172/JCI77685Search in Google Scholar PubMed PubMed Central

Yang, Y., Yin, J., Baumgartner, W., Samapati, R., Solymosi, E.A., Reppien, E., Kuebler, W.M., and Uhlig, S. (2010). Platelet-activating factor reduces endothelial nitric oxide production: role of acid sphingomyelinase. Eur. Respir. J. 36, 417–427.10.1183/09031936.00095609Search in Google Scholar PubMed

Yao, B., Zhang, Y., Sylvie, D., Mathias, S., Basu, S., and Kolesnick, R. (1995). Phosphorylation of Raf by ceramide-activated protein kinase. Nature 378, 307–310.10.1038/378307a0Search in Google Scholar PubMed

Zhang, T. and Saghatelian, A. (2013). Emerging roles of lipids in BCL-2 family-regulated apoptosis. Biochim. Biophys. Acta 1831, 1542–1554.10.1016/j.bbalip.2013.03.001Search in Google Scholar PubMed

Zhang, D.X., Zou, A.P., and Li, P.L. (2001). Ceramide reduces endothelium-dependent vasodilation by increasing superoxide production in small bovine coronary arteries. Circ. Res. 88, 824–831.10.1161/hh0801.089604Search in Google Scholar PubMed

Zhang, Y., Zhang, L., Li, Y., Sun, S., and Tan, H. (2014). Different contributions of clathrin- and caveolae-mediated endocytosis of vascular endothelial cadherin to lipopolysaccharide-induced vascular hyperpermeability. PLoS One 9, e106328.10.1371/journal.pone.0106328Search in Google Scholar PubMed PubMed Central

Zhao, Y., Gorshkova, I.A., Berdyshev, E., He, D., Fu, P., Ma, W., Su, Y., Usatyuk, P.V., Pendyala, S., Oskouian, B., et al. (2011). Protection of LPS-induced murine acute lung injury by sphingosine-1-phosphate lyase suppression. Am. J. Respir. Cell. Mol. Biol. 45, 426–435.10.1165/rcmb.2010-0422OCSearch in Google Scholar PubMed PubMed Central

Zheng, T., Li, W., Wang, J., Altura B.T., and Altura, B.M. (2000). Sphingomyelinase and ceramide analogs induce contraction and rises in [Ca2+]i in canine cerebral vascular muscle. Am. J. Physiol. Heart Circ. Physiol. 278, H1421–H1428.10.1152/ajpheart.2000.278.5.H1421Search in Google Scholar PubMed

Received: 2014-12-9
Accepted: 2015-4-8
Published Online: 2015-5-1
Published in Print: 2015-6-1

©2015 by De Gruyter

Articles in the same Issue

  1. Frontmatter
  2. Guest Editorial
  3. Highlight: Molecular Medicine of Sphingolipids
  4. HIGHLIGHT: MOLECULAR MEDICINE OF SPHINGOLIPIDS
  5. The role of serum amyloid A and sphingosine-1-phosphate on high-density lipoprotein functionality
  6. Sphingolipids in viral infection
  7. Tackling the biophysical properties of sphingolipids to decipher their biological roles
  8. Ceramide and sphingosine in pulmonary infections
  9. Molecular mechanisms of erythrocyte aging
  10. Sphingolipids in liver injury, repair and regeneration
  11. Ultrasound-stimulated microbubble enhancement of radiation response
  12. Innate immune responses in the brain of sphingolipid lysosomal storage diseases
  13. Novel mechanisms of action of classical chemotherapeutic agents on sphingolipid pathways
  14. The role of sphingolipids in endothelial barrier function
  15. The effect of altered sphingolipid acyl chain length on various disease models
  16. Secretory sphingomyelinase in health and disease
  17. Preclinical development of a C6-ceramide NanoLiposome, a novel sphingolipid therapeutic
  18. Sphingomyelin breakdown in T cells: role in activation, effector functions and immunoregulation
  19. The molecular medicine of acid ceramidase
  20. Caenorhabditis elegans as a model to study sphingolipid signaling
  21. S1PR4 is required for plasmacytoid dendritic cell differentiation
  22. Antinociceptive effects of FTY720 during trauma-induced neuropathic pain are mediated by spinal S1P receptors
  23. Subcellular distribution of FTY720 and FTY720-phosphate in immune cells – another aspect of Fingolimod action relevant for therapeutic application
  24. Downregulation of sphingosine 1-phosphate (S1P) receptor 1 by dexamethasone inhibits S1P-induced mesangial cell migration
  25. Sphingosine kinase 2 deficiency increases proliferation and migration of renal mouse mesangial cells and fibroblasts
  26. Obituary
  27. The life and work of Dr. Robert Bittman (1942–2014)
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