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Phenotypic and functional differences between human saphenous vein (HSVEC) and umbilical vein (HUVEC) endothelial cells

      Abstract

      The vascular endothelial cell (EC) plays an essential role in the pathogenesis of inflammation, transplant rejection and tumour metastasis. Most research on vascular ECs uses human umbilical vein endothelial cells (HUVECs). However, HUVECs are derived from immune-naive foetal tissue, and show significant functional differences from adult vascular endothelium. In this paper, we characterise an alternative model based on human saphenous vein ECs (HSVECs), describe their culture conditions and provide a detailed functional comparison with HUVECs. Compared with HUVECs, HSVECs show an increased sensitivity to ox-LDL and a reduced response to cytokines, as indicated by adhesion molecule expression as well as leukocyte adhesion and transmigration. With respect to their ability to present antigen, HSVECs have a higher level of HLA-DR, CD40 and ICOS-L following cytokine stimulation. In addition, HSVECs upregulate the costimulatory ligand CD80 (B7.1) following CD40 ligation, and support allogeneic T cell proliferation, while HUVECs fail to express CD80. Due to differential expression of adhesion molecules, poorly differentiated tumour cell lines also showed more adhesion to HSVECs than to HUVECs. These results indicate that HSVECs have advantages over HUVECs for studying adult vascular endothelial pathology in vitro.

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      References

        • Jaffe E.A
        • Nachman R.L
        • Becker C.G
        • Minick C.R
        Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria.
        J. Clin Invest. 1973; 52: 2745-2756
        • French L.E
        • Hahne M
        • Viard I
        • Radlgruber G
        • Zanone R
        • Becker K
        • et al.
        Fas and Fas ligand in embryos and adult mice: ligand expression in several immune-privileged tissues and coexpression in adult tissues characterized by apoptotic cell turnover.
        J. Cell Biol. 1996; 133: 335-343
        • Guller S
        • LaChapelle L
        The role of placental Fas ligand in maintaining immune privilege at maternal-fetal interfaces.
        Semin Reprod Endocrinol. 1999; 17: 39-44
        • Scoumanne A
        • Kalamati T
        • Moss J
        • Powell J.T
        • Gosling M
        • Carey N
        Generation and characterisation of human saphenous vein endothelial cell lines.
        Atherosclerosis. 2002; 160: 59-67
        • Vergnani L
        • Hatrik S
        • Ricci F
        • Passaro A
        • Manzoli N
        • Zuliani G
        • et al.
        Effect of native and oxidized low-density lipoprotein on endothelial nitric oxide and superoxide production: key role of L-arginine availability.
        Circulation. 2000; 101: 1261-1266
        • Leibovitz A
        • Stinson J.C
        • McCombs III, W.B
        • McCoy C.E
        • Mazur K.C
        • Mabry N.D
        Classification of human colorectal adenocarcinoma cell lines.
        Cancer Res. 1976; 36: 4562-4569
        • von Kleist S
        • Chany E
        • Burtin P
        • King M
        • Fogh J
        Immunohistology of the antigenic pattern of a continuous cell line from a human colon tumor.
        J. Natl Cancer Inst. 1975; 55: 555-560
        • Boyum A
        Isolation of mononuclear cells and granulocytes from human blood. Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g.
        Scand J Clin Lab Invest Suppl. 1968; 97: 77-89
        • Boyum A
        Isolation of leucocytes from human blood. A two-phase system for removal of red cells with methylcellulose as erythrocyte-aggregating agent.
        Scand J Clin Lab Invest Suppl. 1968; 97: 9-29
        • Marelli-Berg F.M
        • Hargreaves R.E
        • Carmichael P
        • Dorling A
        • Lombardi G
        • Lechler R.I
        Major histocompatibility complex class II-expressing endothelial cells induce allospecific nonresponsiveness in naive T cells.
        J. Exp Med. 1996; 183: 1603-1612
        • Zhou L.J
        • Tedder T.F
        CD14+ blood monocytes can differentiate into functionally mature CD83+ dendritic cells.
        Proc Natl Acad Sci USA. 1996; 93: 2588-2592
        • Jollow K.C
        • Zimring J.C
        • Sundstrom J.B
        • Ansari A.A
        CD40 ligation induced phenotypic and functional expression of CD80 by human cardiac microvascular endothelial cells.
        Transplantation. 1999; 68: 430-439
        • Tan P.H
        • Manunta M
        • Ardjomand N
        • Xue S.A
        • Larkin D.F.P
        • Haskard D.O
        • et al.
        Antibody targeted gene transfer to endothelium.
        J. Gene Med. 2003; 5: 311-323
        • Boussiotis V.A
        • Freeman G.J
        • Taylor P.A
        • Berezovskaya A
        • Grass I
        • Blazar B.R
        • et al.
        p27kip1 functions as an anergy factor inhibiting interleukin 2 transcription and clonal expansion of alloreactive human and mouse helper T lymphocytes.
        Nat Med. 2000; 6: 290-297
        • King W.J
        • Comer R.M
        • Hudde T
        • Larkin D.F
        • George A.J
        Cytokine and chemokine expression kinetics after corneal transplantation.
        Transplantation. 2000; 70: 1225-1233
        • Xue S.A
        • Lu Q.L
        • Poulsom R
        • Karran L
        • Jones M.D
        • Griffin B.E
        Expression of two related viral early genes in Epstein–Barr virus-associated tumors.
        J. Virol. 2000; 74: 2793-2803
        • Kuijpers T.W
        • Hakkert B.C
        • Hoogerwerf M
        • Leeuwenberg J.F
        • Roos D
        Role of endothelial leukocyte adhesion molecule-1 and platelet- activating factor in neutrophil adherence to IL-1-prestimulated endothelial cells. Endothelial leukocyte adhesion molecule-1-mediated CD18 activation.
        J. Immunol. 1991; 147: 1369-1376
        • Smith C.W
        • Rothlein R
        • Hughes B.J
        • Mariscalco M.M
        • Rudloff H.E
        • Schmalstieg F.C
        • et al.
        Recognition of an endothelial determinant for CD 18-dependent human neutrophil adherence and transendothelial migration.
        J. Clin Invest. 1988; 82: 1746-1756
        • Hakkert B.C
        • Rentenaar J.M
        • Van Aken W.G
        • Roos D
        • Van Mourik J.A
        A three-dimensional model system to study the interactions between human leukocytes and endothelial cells.
        Eur J Immunol. 1990; 20: 2775-2781
        • Bevilacqua M.P
        • Pober J.S
        • Wheeler M.E
        • Cotran R.S
        • Gimbrone Jr., M.A
        Interleukin 1 acts on cultured human vascular endothelium to increase the adhesion of polymorphonuclear leukocytes, monocytes, and related leukocyte cell lines.
        J. Clin Invest. 1985; 76: 2003-2011
        • Beekhuizen H
        • Blokland I
        • van Furth R
        Cross-linking of CD14 molecules on monocytes results in a CD11/CD18- and ICAM-1-dependent adherence to cytokine-stimulated human endothelial cells.
        J. Immunol. 1993; 150: 950-959
        • Dustin M.L
        • Springer T.A
        Lymphocyte function-associated antigen-1 (LFA-1) interaction with intercellular adhesion molecule-1 (ICAM-1) is one of at least three mechanisms for lymphocyte adhesion to cultured endothelial cells.
        J. Cell Biol. 1988; 107: 321-331
        • Osborn L
        • Hession C
        • Tizard R
        • Vassallo C
        • Luhowskyj S
        • Chi-Rosso G
        • et al.
        Direct expression cloning of vascular cell adhesion molecule 1, a cytokine-induced endothelial protein that binds to lymphocytes.
        Cell. 1989; 59: 1203-1211
        • Carlos T.M
        • Schwartz B.R
        • Kovach N.L
        • Yee E
        • Rosa M
        • Osborn L
        • et al.
        Vascular cell adhesion molecule-1 mediates lymphocyte adherence to cytokine-activated cultured human endothelial cells.
        Blood. 1990; 76: 965-970
        • Oppenheimer-Marks N
        • Davis L.S
        • Lipsky P.E
        Human T lymphocyte adhesion to endothelial cells and transendothelial migration. Alteration of receptor use relates to the activation status of both the T cell and the endothelial cell.
        J. Immunol. 1990; 145: 140-148
        • Oppenheimer-Marks N
        • Davis L.S
        • Bogue D.T
        • Ramberg J
        • Lipsky P.E
        Differential utilization of ICAM-1 and VCAM-1 during the adhesion and transendothelial migration of human T lymphocytes.
        J. Immunol. 1991; 147: 2913-2921
        • Shimizu Y
        • Newman W
        • Gopal T.V
        • Horgan K.J
        • Graber N
        • Beall L.D
        • et al.
        Four molecular pathways of T cell adhesion to endothelial cells: roles of LFA-1, VCAM-1, and ELAM-1 and changes in pathway hierarchy under different activation conditions.
        J. Cell Biol. 1991; 113: 1203-1212
        • Yellin M.J
        • Brett J
        • Baum D
        • Matsushima A
        • Szabolcs M
        • Stern D
        • et al.
        Functional interactions of T cells with endothelial cells: the role of CD40L-CD40-mediated signals.
        J. Exp Med. 1995; 182: 1857-1864
        • Savage C.O
        • Hughes C.C
        • McIntyre B.W
        • Picard J.K
        • Pober J.S
        Human CD4+ T cells proliferate to HLA-DR+ allogeneic vascular endothelium.
        Identification of accessory interactions. Transplantation. 1993; 56: 128-134
        • Page C.S
        • Holloway N
        • Smith H
        • Yacoub M
        • Rose M.L
        Alloproliferative responses of purified CD4+ and CD8+ T cells to endothelial cells in the absence of contaminating accessory cells.
        Transplantation. 1994; 57: 1628-1637
        • Kreisel D
        • Krupnick A.S
        • Gelman A.E
        • Engels F.H
        • Popma S.H
        • Krasinskas A.M
        • et al.
        Non-hematopoietic allograft cells directly activate CD8+ T cells and trigger acute rejection: an alternative mechanism of allorecognition.
        Nat Med. 2002; 8: 233-239
        • Raab M
        • Daxecker H
        • Markovic S
        • Karimi A
        • Griesmacher A
        • Mueller M.M
        Variation of adhesion molecule expression on human umbilical vein endothelial cells upon multiple cytokine application.
        Clin Chim Acta. 2002; 321: 11-16
        • Printseva O
        • Peclo M.M
        • Gown A.M
        Various cell types in human atherosclerotic lesions express ICAM-1. Further immunocytochemical and immunochemical studies employing monoclonal antibody 10F3.
        Am J Pathol. 1992; 140: 889-896
        • Napoli C
        • D’Armiento F.P
        • Mancini F.P
        • Postiglione A
        • Witztum J.L
        • Palumbo G
        • et al.
        Fatty streak formation occurs in human fetal aortas and is greatly enhanced by maternal hypercholesterolemia. Intimal accumulation of low density lipoprotein and its oxidation precede monocyte recruitment into early atherosclerotic lesions.
        J. Clin Invest. 1997; 100: 2680-2690
        • Thornhill M.H
        • Kyan-Aung U
        • Haskard D.O
        IL-4 increases human endothelial cell adhesiveness for T cells but not for neutrophils.
        J. Immunol. 1990; 144: 3060-3065
        • Thornhill M.H
        • Wellicome S.M
        • Mahiouz D.L
        • Lanchbury J.S
        • Kyan-Aung U
        • Haskard D.O
        Tumor necrosis factor combines with IL-4 or IFN-gamma to selectively enhance endothelial cell adhesiveness for T cells. The contribution of vascular cell adhesion molecule-1-dependent and -independent binding mechanisms.
        J. Immunol. 1991; 146: 592-598
        • Hakkert B.C
        • Kuijpers T.W
        • Leeuwenberg J.F
        • van Mourik J.A
        • Roos D
        Neutrophil and monocyte adherence to and migration across monolayers of cytokine-activated endothelial cells: the contribution of CD18, ELAM-1, and VLA-4.
        Blood. 1991; 78: 2721-2726
        • Kyan-Aung U
        • Haskard D.O
        • Poston R.N
        • Thornhill M.H
        • Lee T.H
        Endothelial leukocyte adhesion molecule-1 and intercellular adhesion molecule-1 mediate the adhesion of eosinophils to endothelial cells in vitro and are expressed by endothelium in allergic cutaneous inflammation in vivo.
        J. Immunol. 1991; 146: 521-528
        • Honda H.M
        • Leitinger N
        • Frankel M
        • Goldhaber J.I
        • Natarajan R
        • Nadler J.L
        • et al.
        Induction of monocyte binding to endothelial cells by MM-LDL: role of lipoxygenase metabolites.
        Arterioscler Thromb Vasc Biol. 1999; 19: 680-686
        • Muller W.A
        • Weigl S.A
        Monocyte-selective transendothelial migration: dissection of the binding and transmigration phases by an in vitro assay.
        J. Exp Med. 1992; 176: 819-828
        • Skalen K
        • Gustafsson M
        • Rydberg E.K
        • Hulten L.M
        • Wiklund O
        • Innerarity T.L
        • et al.
        Subendothelial retention of atherogenic lipoproteins in early atherosclerosis.
        Nature. 2002; 417: 750-754
        • Zhang S
        • Day I
        • Ye S
        Nicotine induced changes in gene expression by human coronary artery endothelial cells.
        Atherosclerosis. 2001; 154: 277-283
        • Shih P.T
        • Elices M.J
        • Fang Z.T
        • Ugarova T.P
        • Strahl D
        • Territo M.C
        • et al.
        Minimally modified low-density lipoprotein induces monocyte adhesion to endothelial connecting segment-1 by activating beta1 integrin.
        J. Clin Invest. 1999; 103: 613-625
        • Groves R.W
        • Allen M.H
        • Barker J.N
        • Haskard D.O
        • MacDonald D.M
        Endothelial leucocyte adhesion molecule-1 (ELAM-1) expression in cutaneous inflammation.
        Br J Dermatol. 1991; 124: 117-123
        • Goda K
        • Tanaka T
        • Monden M
        • Miyasaka M
        Characterization of an apparently conserved epitope in E- and P-selectin identified by dual-specific monoclonal antibodies.
        Eur J Immunol. 1999; 29: 1551-1560
        • Wellicome S.M
        • Thornhill M.H
        • Pitzalis C
        • Thomas D.S
        • Lanchbury J.S
        • Panayi G.S
        • 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
        • Wellicome S.M
        • Kapahi P
        • Mason J.C
        • Lebranchu Y
        • Yarwood H
        • Haskard D.O
        Detection of a circulating form of vascular cell adhesion molecule-1: raised levels in rheumatoid arthritis and systemic lupus erythematosus.
        Clin Exp Immunol. 1993; 92: 412-418