Abstract
Research over the last two decades has produced major insights into the role of vascular endothelium in the orchestration of inflammatory responses. Endothelial cells play an active part in a variety of inflammatory and thrombotic processes, not least in the recruitment of leukocytes from the blood into surrounding tissues.1 This chapter focuses on the role in inflammation of a particular endothelial surface glycoprotein, E-selectin, which acts as an inducible adhesion molecule for leukocytes and as an excellent reporter of endothelial cell (EC) activation.
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References
Cines DB, Pollak ES, Buck CA, et al. Endothelial cells in physiology and in the pathophysiology of vascular disorders. Blood 1998;91:3527–3561.
Jaffe EA, Nachman RL, Becker CG, Minick CR. Culture of human endothelial cells derived from umbilical veins. J Clin Invest 1973;52:2745–2756.
Pober JS, Cotran RS. Cytokines and endothelial cell biology. Physiolog Rev 1990;70:427–451.
Mayer H, Bilban M, Kurtev V, et al. Deciphering regulatory patterns of inflammatory gene expression from interleukin-1-stimulated human endothelial cells. Arterioscler Thromb Vasc Biol 2004;24(7):1192–1198.
Bevilacqua MP, Pober JS, Mendrick DL, Cotran RS, Gimbrone MA. Identification of an inducible endothelial-leukocyte adhesion molecule. Proc Natl Acad Sci USA 1987;84:9238–9242.
Anderson DC, Lasky L, Butcher EC, et al. Peripheral lymph node homing receptor (LECAM-1). Immunol Today 1991;12:216.
McEver RP, Beckstead JH, Moore KL, Marshall-Carlson L, Bainton DF. GMP-140, a platelet α-granule membrane protein, is also synthesized by vascular endothelial cells and is localized in Weibel-Palade bodies. J Clin Invest 1989;84:92–99.
Larsen E, Celi A, Gilbert GE, et al. PADGEM protein: a receptor that mediates the interaction of activated platelets with neutrophils and monocytes. Cell 1989;59:305–312.
Watson ML, Kingsmore SF, Johnston GI, et al. Genomic organization of the selectin family of leukocyte adhesion molecules on human and mouse chromosome 1. J Exp Med 1990;172:263–272.
Collins T, Williams A, Johnston GI, et al. Structure and chromosomal location of the gene for endothelial-leukocyte adhesion molecule 1. J Biol Chem 1991;266:2466–2473.
Kansas GS. Selectins and their ligands: current concepts and controversies. Blood 1996;88(9):3259–3287.
Vestweber D, Blanks JE. Mechanisms that regulate the function of the selectins and their ligands. Physiolog Rev 1999;79:181–213.
McEver RP. Selectins: lectins that initiate cell adhesion under flow. Curr Opin Cell Biol 2002;14(5):581–586.
Graves BJ, Crowther RL, Chandran C, et al. Insight from E-selectin/ligand interaction from the crystal structure and mutagenesis of the lec/EGF domains. Nature 1994;367:532–538.
Alon R, Hammer DA, Springer TA. Lifetime of the P-selectin-carbohydrate bond and its response to tensile force in hydrodymanic flow. Nature 1995;374:539–542.
Lawrence MB, Kansas GS, Kunkel EJ, Ley K. Threshold levels of fluid shear promote leukocyte adhesion through selectins (CD62L,P,E). J Cell Biol 1997;136(3):717–727.
Phan UT, Waldron TT, Springer TA. Remodeling of the lectin-EGF-like domain interface in P-and L-selectin increases adhesiveness and shear resistance under hydrodynamic force. Nat Immunol 2006;7(8):883–889.
Chen S, Alon R, Fuhlbrigge RC, Springer TA. Rolling and transient tethering of leukocytes on antibodies reveal specializations of selectins. Proc Natl Acad Sci USA 1997;94(7):3172–3177.
McArthur JC, Griffin JW, Cornblath DR, et al. Steroid-responsive myeloneuropathy in a man dually infected with HIV-1 and HTLV-1. Neurology 1990;40:938.
Lawrence MB, Springer TA. Leukocytes roll on a selectin at physiologic flow rates: distinction from and prerequisite for adhesion through integrins. Cell 1991;65(5):859–873.
Springer TA. Traffic signals on endothelium for lymphocyte recirculation and leukocyte emigration. Annu Rev Physiol 1995;57:827–872.
Lowe JB. Glycan-dependent leukocyte adhesion and recruitment in inflammation. Curr Opin Cell Biol 2003;15(5):531–538.
Zollner O, Lenter MC, Blanks JE, et al. L-selectin from human, but not from mouse neutrophils binds directly to E-selectin. J Cell Biol 1997;136(3):707–715.
Kotovuori P, Tontti E, Pigott R, et al. The vascular E-selectin binds to the leukocyte integrins CD11/CD18. Glycobiology 1993;3:131–136.
Katayama Y, Hidalgo A, Chang J, Peired A, Frenette PS. CD44 is a physiological Eselectin ligand on neutrophils. J Exp Med 2005;201(8):1183–1189.
Steegmaler M, Levinovitz A, Isenmann S, et al. The E-selectin-ligand ESL-1 is a variant of a receptor for fibroblast growth factor. Nature 1995;373:615–620.
Lawrence MB, Bainton DF, Springer TA. Neutrophil tethering to and rolling on Eselectin are separable by requirement for L-selectin. Immunity 1994;1:137–145.
Patel KD, Moore KL, Nollert MU, McEver RP. Neutrophils use both shared and distinct mechanisms to adhere to selectins under static and flow conditions. J Clin Invest 1995;96(4):1887–1896.
Xia L, Sperandio M, Yago T, et al. P-selectin glycoprotein ligand-1-deficient mice have impaired leukocyte tethering to E-selectin under flow. J Clin Invest 2002;109(7):939–950.
Lawrence MB, Springer TA. Neutrophils roll on E-selectin. J Immunol 1993;151:6338–6346.
Graber N, Gopal TV, Wilson D, Beall LD, Polte T, Newman W. T cells bind to cytokine-activated endothelial cells via a novel, inducible sialoglycoprotein and endothelial leukocyte adhesion molecule-1. J Immunol 1990;145:819–830.
Picker LJ, Kishimoto TK, Smith CW, Warnock RA, Butcher EC. ELAM-1 is an adhesion molecule for skin-homing T cells. Nature 1991;349:796–799.
Berg EL, Yoshino T, Rott LS, et al. The cutaneous lymphocyte antigen is a skin lymphocyte homing receptor for the vascular lectin endothelial cell-leukocyte adhesion molecule 1. J Exp Med 1991;174:1461–1466.
Fuhlbrigge RC, Kieffer JD, Armerding D, Kupper TS. Cutaneous lymphocyte antigen is a specialized form of PSGL-1 expressed on skin-homing T cells. Nature 1997;389:978–981.
Knibbs RN, Craig RA, Natsuka S, et al. The fucosyltransferase FucT-VII regulates E-selectin ligand synthesis in human T cells. J Cell Biol 1996;133(4):911–920.
Knibbs RN, Craig RA, Mály P, et al. α(1,3)-Fucosyltransferase VII-dependent synthesis of P-and E-selectin ligands on cultured T lymphoblasts. J Immunol 1998;161:6305–6315.
Picker LJ, Michie SA, Rott LS, Butcher EC. A unique phenotype of skin-associated lymphocytes in humans. Preferential expression of the HECA-452 epitope by benign and malignant T cells at cutaneous sites. Am J Pathol 1990;136:1053–1068.
Campbell JJ, Haraldsen G, Pan J, et al. The chemokine receptor CCR4 in vascular recognition by cutaneous but not intestinal memory T cells. Nature 1999;400:776–780.
Diacovo TG, Roth SJ, Morita CT, Rosat J-P, Brenner MB, Springer TA. Interactions of human alpha/beta and gamma/delta T lymphocyte subsets in shear flow with E-selectin and P-selectin. J Exp Med 1996;183:1193–1203.
Austrup F, Vestweber D, Borges E, et al. P-and E-selectin mediate recruitment of T-helper-1 but not T-helper-2 cells into inflammed tissues. Nature 1997;385(6611):81–83.
Xie H, Lim YC, Luscinskas FW, Lichtman AH. Acquisition of selectin binding and peripheral homing properties by CD4+ and CD8+ T cells. J Exp Med 1999;189 (No 11):1765–1775.
Hattori R, Hamilton KK, Fugate RD, McEver RD, Sims PJ. Stimulated secretion of endothelial von Willebrand factor is accompanied by rapid redistribution to the cell surface of the intracellular granule membrane protein GMP-140. J Biol Chem 1989;264:7768–7771.
Utgaard JO, Jahnsen FL, Bakka A, Brandtzaeg P, Haraldsen G. Rapid secretion of prestored interleukin 8 from Weibel-Palade bodies of microvascular endothelial cells. J Exp Med 1998;188(9):1751–1756.
Wolff B, Burns AR, Middleton J, Rot A. Endothelial cell “memory” of inflammatory stimulation: human venular endothelial cells store interleukin 8 in Weibel-Palade bodies. J Exp Med 1998;188(9):1757–1762
Green SA, Setiadi H, McEver RP, Kelly RB. The cytoplasmic domain of P-selectin contains a sorting determinant that mediates rapid degradation in lysosomes. J Cell Biol 1994;124:435–448.
Subramaniam M, Koedam JA, Wagner DD. Divergent fates of P-selectin and Eselectin after their expression on the plasma membrane. Mol Biol Cell 1993;4:791–801.
Kempe S, Kestler H, Lasar A, Wirth T. NF-KappaB controls the global pro-inflammatory response in endothelial cells: evidence for the regulation of a pro-atherogenic program. Nucleic Acids Res 2005;33(16):5308–5319.
Pober JS, Bevilacqua MP, Mendrick DL, Lapierre LA, Fiers W, Gimbrone MA. Two distinct monokines, interleukin 1 and tumor necrosis factor, each independently induce the biosynthesis and transient expression of the same antigen on the surface of cultured human vascular endothelial cells. J Immunol 1986;136:1680–1687.
Wellicome SM, Thornhill MH, Pitzalis C, et al. A monoclonal antibody that detects a novel antigen on endothelial cells that is induced by tumor necrosis factor, IL-1 or lipopolysaccharide. J Immunol 1990;144:2558–2565.
Smith GM, Whelan J, Pescini R, Ghersa P, DeLamarter JF, Hooft van Huijsduijnen R. DNA-methylation of the E-selectin promoter represses NF-kappaB transactivation. Biochem Biophys Res Commun 1993;194:215–221.
Schindler U, Baichwal VR. Three NK-kappa B binding sites in the human E-selectin gene required for maximal tumor necrosis factor alpha-induced expression. Mol Cell Biol 1994;14:5820–5831.
Lewis H, Kaszubska W, DeLamarter JF, Whelan J. Cooperativity between two NF-kappa B complexes, mediated by high mobility-group protein I(Y), is essential for cytokine-induced expression of the E-selectin promoter. Mol Cell Biol 1994;14:5701–5709.
Whelan J, Ghersa P, Hooft van Huijsduijnen R, et al. An NFkB-like factor is essential but not sufficient for cytokine induction of endothelial leukocyte adhesion molecule 1 (ELAM-1) gene transcription. Nucleic Acids Res 1991;19(10):2645–2653.
Whitley MZ, Thanos D, Read MA, Maniatis T, Collins T. A striking similarity in the organization of the E-selectin and beta interferon gene promoters. Mol Cell Biol 1994;14:6464–6475.
Gerritsen ME, Williams AJ, Neish AS, Moore S, Shi Y, Collins T. CREB-binding protein/p300 are transcriptional coactivators of p65. Proc Natl Acad Sci USA 1997;94(7):2927–2932.
Sheppard KA, Rose DW, Haque ZK, et al. Transcriptional activation by NF-kappaB requires multiple coactivators. Mol Cell Biol 1999;19(9):6367–6378.
Edelstein LC, Pan A, Collins T. Chromatin modification and the endothelialspecific activation of the E-selectin gene. J Biol Chem 2005;280(12):11192–11202.
Min W, Pober JS. TNF initiates E-selectin transcription in human endothelial cells through parallel TRAF-NF-kappa B and TRAF-RAC/CDC42-JNK-c-Jun/ATF2 pathways. J Immunol 1997;159(7):3508–3518.
Hooft van Huijsduijnen R, Whelan J, Pescini R, Becker-André M, Schenk A-M, DeLamarter JF. A T-cell enhancer cooperates with NF-kappaB to yield cytokine induction of E-selectin gene transcription in endothelial cells. J Biol Chem 1992;267:22385–22391.
Kaszubska W, Hooft van HR, Ghersa P, et al. Cyclic AMP-independent ATF family members interact with NF-kappa B and function in the activation of the E-selectin promoter in response to cytokines. Mol Cell Biol 1993;13(11):7180–7190.
De Luca LG, Johnson DR, Whitley MZ, Collins T, Pober JS. cAMP and tumor necrosis factor competitively regulate transcriptional activation through and nuclear factor binding to the cAMP-responsive element/activating transcription factor element of the endothelial leukocyte adhesion molecule-1 (E-selectin) promoter. J Biol Chem 1994;269:19193–19196.
Meacock S, Pescini-Gobert R, DeLamarter JF, Hooft van Huijsduijnen R. Transcription factor-induced, phased bending of the E-selectin promoter. J Biol Chem 1994;269:31756–31762.
Read MA, Whitley MZ, Gupta S, et al. Tumor necrosis factor alpha-induced E-selectin expression is activated by the nuclear factor-kappaB and c-JUN N-terminal kinase/p38 mitogen-activated protein kinase pathways. J Biol Chem 1997;272(5):2753–2761.
Ghersa P, Hooft van HR, Whelan J, DeLamarter JF. Labile proteins play a dual role in the control of endothelial leukocyte adhesion molecule-1 (ELAM-1) gene regulation. J Biol Chem 1992;267(27):19226–19232.
von Asmuth EJU, Smeets EF, Ginsel LA, Onderwater JJM, Leeuwenberg JFM, Buurman WA. Evidence for endocytosis of E-selectin in human endothelial cells. Eur J Immunol 1992;22:2519–2526.
Chu W, Presky DH, Swerlick RAr, Burns DK. Alternatively processed human E-selectin transcripts linked to chronic expression of E-selectin in vivo. J Immunol 1996;153:4179–4189.
De Martin R, Vanhove B, Cheng Q, et al. Cytokine-inducible expression in endothelial cells of an IκBα-like gene is regulated by NFκB. EMBO J 1993;12:2773–2779.
Cooper JT, Stroka DM, Brostjan C, Palmetshofer A, Bach FH, Ferran C. A20 blocks endothelial cell activation through a NF-kappaB-dependent mechanism. J Biol Chem 1996;271(30):18068–18073.
Johnson DR, Douglas I, Jahnke A, Ghosh S, Pober JS. A sustained reduction in IkB-B may contribute to persistent NK-kB activation in human endothelial cells. J Biol Chem 1996;271:16317–16322.
Petzelbauer P, Bender JR, Wilson J, Pober JS. Heterogeneity of dermal microvascular endothelial cell antigen expression and cytokine responsiveness in situ and in cell culture. J Immunol 1993;151:5062–5072.
Rohde D, Schluter-Wigger W, Mielke V, von den D P, von G B, Sterry W. Infiltration of both T cells and neutrophils in the skin is accompanied by the expression of endothelial leukocyte adhesion molecule-1 (ELAM-1): an immunohistochemical and ultrastructural study. J Invest Dermatol 1992;98(5):794–799.
Kluger MS, Johnson DR, Pober JS. Mechanism of sustained E-selectin expression in cultured human dermal microvascular endothelial cells. J Immunol 1997;158:887–896.
Kluger MS, Shiao SL, Bothwell AL, Pober JS. Cutting edge: internalization of transduced E-selectin by cultured human endothelial cells: comparison of dermal microvascular and umbilical vein cells and identification of a phosphoserine-type di-leucine motif. J Immunol 2002;168(5):2091–2095.
Topper JN, Cai J, Falb D, Gimbrone MA, Jr. Identification of vasculalr endothelial genes differentially responsive to fluid mechanical stimuli: cyclooxygenase-2, managanese superooxide dismutase, and endothelial cell nitric oxide synthase are selectively up-regulated by steady laminar shear stress. Proc Natl Acad Sci USA 1996;93:10417–10422.
Dai G, Kaazempur-Mofrad MR, Natarajan S, et al. Distinct endothelial phenotypes evoked by arterial waveforms derived from atherosclerosis-susceptible and-resistant regions of human vasculature. Proc Natl Acad Sci USA 2004;101(41):14871–14876.
Chiu JJ, Lee PL, Chen CN, et al. Shear stress increases ICAM-1 and decreases VCAM-1 and E-selectin expressions induced by tumor necrosis factor-[alpha] in endothelial cells. Arterioscler Thromb Vasc Biol 2004;24(1):73–79.
Surapisitchat J, Hoefen RJ, Pi X, Yoshizumi M, Yan C, Berk BC. Fluid shear stress inhibits TNF-alpha activation of JNK but not ERK1/2 or p38 in human umbilical vein endothelial cells: Inhibitory crosstalk among MAPK family members. Proc Natl Acad Sci USA 2001;98(11):6476–6481.
Hajra L, Evans AI, Chen M, Hyduk SJ, Collins T, Cybulsky MI. The NF-κB signal tranduction pathway in aortic endothelial cells is primed for activation in regions predisposed to atherosclerotic lesion formation. Proc Natl Acad Sci USA 2001;97:9052–9057.
Cotran RS, Gimbrone MA, Bevilacqua MP, Mendrick DL, Pober JS. Induction and detection of a human endothelial activation antigen in vivo. J Exp Med 1986;164:661–666.
Norris P, Poston RN, Thomas DS, Thornhill M, Hawk J, Haskard DO. The expression of endothelial leukocyte adhesion molecule-1 (ELAM-1), Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in experimental cutaneous inflammation: a comparison of ultraviolet-B erythema and delayed hypersensitivity. J Invest Dermatol 1991;96:763–770.
Keelan ETM, Licence ST, Peters AM, Binns RM, Haskard DO. Characterization of E-selectin expression in vivo using a radiolabeled monoclonal antibody. Am J Physiol 1994;266:H279–H290.
Binns RM, Licence ST, Harrison AA, Keelan ETD, Robinson MK, Haskard DO. In vivo E-selectin upregulation correlates with early infiltration of PMN, later with PBL-entry: mAbs block both. Am J Physiol 1996;270:H183–H193.
Binns RM, Whyte A, Licence ST, et al. The role of E-selectin in lymphocyte and polymorphonuclear cell recruitment into cutaneous delayed hypersensitivity reactions in sensitized pigs. J Immunol 1996;157:4094–4099.
Harrison AA, Stocker CJ, Chapman PT, et al. Expression of vascular cell adhesion molecule-1 by vascular endothelial cells in immune and nonimmune inflammatory reactions in the skin. J Immunol 1997;159(9):4546–4554.
Harari O, McHale J, Marshall D, et al. Endothelial cell E-and P-selectin up-regulation in murine contact sensitivity is prolonged by distinct mechanisms occurring in sequence. J Immunol 1999;163(12):6860–6866.
Pan J, Xia L, McEver RP. Comparison of promoters for the murine and human P-selectin genes suggests species-specific and conserved mechanisms for transcriptional regulation in endothelial cells. J Biol Chem 1998;273(16):10058–10067.
Yao L, Pan J, Setiadi H, Patel KD, McEver RP. Interleukin 4 or oncostatin M induces a prolonged increase in P-selectin mRNA and protein in human endothelial cells. J Exp Med 1996;184(1):81–92.
Mchale JF, Harari OA, Marshall D, Haskard DO. TNFalpha and IL-1 sequentially induce endothelial ICAM-1 and VCAM-1 expression in MRL/lpr lupus-prone mice. J Immunol 1999;163(7):3993–4000.
Marshall D, Dangerfield JP, Bhatia V, Larbi K, Nourshargh S, Haskard DO. MRL/lpr lupus-prone mice show exaggerated ICAM-1 dependent leukocyte adhesion and transendothelial migration in response to TNFα. Rheumatology 2003;42:929–934.
Harari O, Marshall D, McHale J, Ahmed S, Haskard DO. Limited endothelial E-and P-selectin expression in MRL/lpr lupus-prone mice. Rheumatology 2001;40:889–895.
Keelan ETM, Harrison AA, Chapman PT, Binns RM, Peters AM, Haskard DO. Imaging vascular endothelial activation: an approach using radiolabeled monoclonal antibody against the endothelial cell adhesion molecule E-selectin. J Nucl Med 1994;35:276–281.
Jamar F, Chapman PT, Harrison AA, Binns RM, Haskard DO, Peters AM. Inflammatory arthritis: imaging of endothelial activation with an indium-111-labeled F(ab′)2 fragment of anti-E-selectin monoclonal antibody. Radiology 1995;194:843–850.
Chapman PT, Jamar F, Harrison AA, Binns RM, Peters AM, Haskard DO. Noninvasive imaging of E-selectin expression by activated endothelium in urate crystal-induced arthritis. Arthritis Rheum 1994;37:1752–1756.
Chapman PT, Yarwood H, Harrison AA, et al. Endothelial activation in monosodium urate monohydrate crystal-induced inflammation: in vitro and in vivo studies on the roles of tumor necrosis factor-alpha and interleukin-1. Arthritis Rheum 1997;40(5):955–965.
Chapman PT, Jamar F, Keelan ETM, Peters AM, Haskard DO. Use of a radiolabeled monoclonal antibody against E-selectin for imaging endothelial activation in rheumatoid arthritis. Arthritis Rheum 1996;39:1371–1375.
Jamar F, Houssiau FA, Devogelaer JP, et al. Scintigraphy using a technetium 99m-labeled anti-E-selectin Fab fragment in rheumatoid arthritis. Rheumatology (Oxford) 2002;41(1):53–61.
Malik IS, Al-Nahhas A, Peters AM, Haskard DO. Imaging musculoskeletal infection with 111indium labeled anti-E-selectin monoclonal antibody 1.2B6 as an alternative to 111indium labeled leukocyte scintigraphy. Arthritis Rheum 2004;50:S263 (abstr 588).
Bhatti M, Chapman P, Peters AM, Haskard DO, Hodgson H. Visualizing E-selectin in the detection and evaluation of inflammatory bowel disease. Gut 1998;43:40–47.
Reynolds PR, Larkman DJ, Haskard DO, Hajnal JV, George AJT, Edwards AD. Detection of vascular expression of E-selectin in vivo by MR imaging. Radiology 2006;241:469–476.
Bhushan M, Bleiker TO, Ballsdon AE, et al. Anti-E-selectin is ineffective in the treatment of psoriasis: a randomized trial. Br J Dermatol 2002;146(5):824–831.
Spragg DD, Alford DR, Greferath R, et al. Immunotargeting of liposomes to activated vascular endothelial cells: a strategy for site-selective delivery in the cardiovascular system. Proc Natl Acad Sci USA 1997;94:8795–8800.
Harari OA, Wickham TJ, Stocker CJ, et al. Targeting an adenoviral gene vector to cytokine-activated vascular endothelium via E-selectin. Gene Ther 1999;6(5):801–807.
Everts M, Kok RJ, Asgeirsdottir SA, et al. Selective intracellular delivery of dexamethasone into activated endothelial cells using an E-selectin-directed immunoconjugate. J Immunol 2002;168(2):883–889.
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Haskard, D.O. (2008). Endothelial Activation in Inflammation: Lessons Learned from E-Selectin. In: Abraham, D., Dashwood, M., Handler, C., Coghlan, G. (eds) Vascular Complications in Human Disease. Springer, London. https://doi.org/10.1007/978-1-84628-919-4_6
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