1.Knolle PA, Wohlleber D. Immunological functions of liver sinusoidal endothelial cells. Cell Mol Immunol. 2016;13(3):347–53.
2.Shetty S, Lalor PF, Adams DH. Liver sinusoidal endothelial cells - gatekeepers of hepatic immunity. Nat Rev Gastroenterol Hepatol. 2018;15(9):555–67.
3.Bilzer M, Roggel F, Gerbes AL. Role of Kupffer cells in host defense and liver disease. Liver Int. 2006;26(10):1175–86.
4.van Furth R, Cohn ZA, Hirsch JG, Humphrey JH, Spector WG, Langevoort HL. The mononuclear phagocyte system: a new classification of macrophages, monocytes, and their precursor cells. Bulletin of the World Health Organization. 1972;46(6):845–52.
5.Sorensen KK, McCourt P, Berg T, Crossley C, Le Couteur D, Wake K, et al. The scavenger endothelial cell: a new player in homeostasis and immunity. Am J Physiol Regul Integr Comp Physiol. 2012;303(12):R1217–30.
6.Seternes T, Sorensen K, Smedsrod B. Scavenger endothelial cells of vertebrates: a nonperipheral leukocyte system for high-capacity elimination of waste macromolecules. Proc Natl Acad Sci U S A. 2002;99(11):7594–7.
7.Eriksson S, Fraser JR, Laurent TC, Pertoft H, Smedsrod B. Endothelial cells are a site of uptake and degradation of hyaluronic acid in the liver. Exp Cell Res. 1983;144(1):223–8.
8.Skogh T, Blomhoff R, Eskild W, Berg T. Hepatic uptake of circulating IgG immune complexes. Immunology. 1985;55(4):585–94.
9.Smedsrod B, Johansson S, Pertoft H. Studies in vivo and in vitro on the uptake and degradation of soluble collagen alpha 1(I) chains in rat liver endothelial and Kupffer cells. Biochem J. 1985;228(2):415–24.
10.Melkko J, Hellevik T, Risteli L, Risteli J, Smedsrod B. Clearance of NH2-terminal propeptides of types I and III procollagen is a physiological function of the scavenger receptor in liver endothelial cells. J Exp Med. 1994;179(2):405–12.
11.Smedsrod B, Melkko J, Araki N, Sano H, Horiuchi S. Advanced glycation end products are eliminated by scavenger-receptor-mediated endocytosis in hepatic sinusoidal Kupffer and endothelial cells. Biochem J. 1997;322 ( Pt 2):567–73.
12.Smedsrod B, Einarsson M. Clearance of tissue plasminogen activator by mannose and galactose receptors in the liver. Thromb Haemost. 1990;63(1):60–6.
13.Smedsrod B, Melkko J, Risteli L, Risteli J. Circulating C-terminal propeptide of type I procollagen is cleared mainly via the mannose receptor in liver endothelial cells. Biochem J. 1990;271(2):345–50.
14.Dahl LB, Laurent TC, Smedsrod B. Preparation of biologically intact radioiodinated hyaluronan of high specific radioactivity: coupling of 125I-tyramine-cellobiose to amino groups after partial N-deacetylation. Anal Biochem. 1988;175(2):397–407.
15.Smedsrod B, Pertoft H, Gustafson S, Laurent TC. Scavenger functions of the liver endothelial cell. Biochem J. 1990;266(2):313–27.
16.Sorensen KK, Simon-Santamaria J, McCuskey RS, Smedsrod B. Liver Sinusoidal Endothelial Cells. Compr Physiol. 2015;5(4):1751–74.
17.Malovic I, Sorensen KK, Elvevold KH, Nedredal GI, Paulsen S, Erofeev AV, et al. The mannose receptor on murine liver sinusoidal endothelial cells is the main denatured collagen clearance receptor. Hepatology. 2007;45(6):1454–61.
18.Elvevold K, Simon-Santamaria J, Hasvold H, McCourt P, Smedsrod B, Sorensen KK. Liver sinusoidal endothelial cells depend on mannose receptor-mediated recruitment of lysosomal enzymes for normal degradation capacity. Hepatology. 2008;48(6):2007–15.
19.Ganesan LP, Mohanty S, Kim J, Clark KR, Robinson JM, Anderson CL. Rapid and efficient clearance of blood-borne virus by liver sinusoidal endothelium. PLoS Pathog. 2011;7(9):e1002281.
20.Simon-Santamaria J, Rinaldo CH, Kardas P, Li R, Malovic I, Elvevold K, et al. Efficient uptake of blood-borne BK and JC polyomavirus-like particles in endothelial cells of liver sinusoids and renal vasa recta. PLoS One. 2014;9(11):e111762.
21.Mates JM, Yao Z, Cheplowitz AM, Suer O, Phillips GS, Kwiek JJ, et al. Mouse Liver Sinusoidal Endothelium Eliminates HIV-Like Particles from Blood at a Rate of 100 Million per Minute by a Second-Order Kinetic Process. Front Immunol. 2017;8(35):35.
22.Simon-Santamaria J, Malovic I, Warren A, Oteiza A, Le Couteur D, Smedsrod B, et al. Age-related changes in scavenger receptor-mediated endocytosis in rat liver sinusoidal endothelial cells. J Gerontol A Biol Sci Med Sci. 2010;65(9):951–60.
23.Godfrey C, Desviat LR, Smedsrod B, Pietri-Rouxel F, Denti MA, Disterer P, et al. Delivery is key: lessons learnt from developing splice-switching antisense therapies. EMBO Mol Med. 2017;9(5):545–57.
24.McCourt PA, Smedsrod BH, Melkko J, Johansson S. Characterization of a hyaluronan receptor on rat sinusoidal liver endothelial cells and its functional relationship to scavenger receptors. Hepatology. 1999;30(5):1276–86.
25.Politz O, Gratchev A, McCourt PA, Schledzewski K, Guillot P, Johansson S, et al. Stabilin–1 and –2 constitute a novel family of fasciclin-like hyaluronan receptor homologues. Biochem J. 2002;362(Pt 1):155–64.
26.Mousavi SA, Sporstol M, Fladeby C, Kjeken R, Barois N, Berg T. Receptor-mediated endocytosis of immune complexes in rat liver sinusoidal endothelial cells is mediated by FcgammaRIIb2. Hepatology. 2007;46(3):871–84.
27.Uhrig A, Banafsche R, Kremer M, Hegenbarth S, Hamann A, Neurath M, et al. Development and functional consequences of LPS tolerance in sinusoidal endothelial cells of the liver. J Leukoc Biol. 2005;77(5):626–33.
28.Martin-Armas M, Simon-Santamaria J, Pettersen I, Moens U, Smedsrod B, Sveinbjornsson B. Toll-like receptor 9 (TLR9) is present in murine liver sinusoidal endothelial cells (LSECs) and mediates the effect of CpG-oligonucleotides. J Hepatol. 2006;44(5):939–46.
29.Wu J, Meng Z, Jiang M, Zhang E, Trippler M, Broering R, et al. Toll-like receptor-induced innate immune responses in non-parenchymal liver cells are cell type-specific. Immunology. 2010;129(3):363–74.
30.Knolle PA, Germann T, Treichel U, Uhrig A, Schmitt E, Hegenbarth S, et al. Endotoxin down-regulates T cell activation by antigen-presenting liver sinusoidal endothelial cells. J Immunol. 1999;162(3):1401–7.
31.Limmer A, Ohl J, Kurts C, Ljunggren HG, Reiss Y, Groettrup M, et al. Efficient presentation of exogenous antigen by liver endothelial cells to CD8+ T cells results in antigen-specific T-cell tolerance. Nat Med. 2000;6(12):1348–54.
32.Limmer A, Ohl J, Wingender G, Berg M, Jungerkes F, Schumak B, et al. Cross-presentation of oral antigens by liver sinusoidal endothelial cells leads to CD8 T cell tolerance. Eur J Immunol. 2005;35(10):2970–81.
33.Steffan AM, Gendrault JL, McCuskey RS, McCuskey PA, Kirn A. Phagocytosis, an unrecognized property of murine endothelial liver cells. Hepatology. 1986;6(5):830–6.
34.Chi JT, Chang HY, Haraldsen G, Jahnsen FL, Troyanskaya OG, Chang DS, et al. Endothelial cell diversity revealed by global expression profiling. Proc Natl Acad Sci U S A. 2003;100(19):10623–8.
35.Nolan DJ, Ginsberg M, Israely E, Palikuqi B, Poulos MG, James D, et al. Molecular signatures of tissue-specific microvascular endothelial cell heterogeneity in organ maintenance and regeneration. Dev Cell. 2013;26(2):204–19.
36.DeLeve LD, Maretti-Mira AC. Liver Sinusoidal Endothelial Cell: An Update. Semin Liver Dis. 2017;37(4):377–87.
37.Elvevold K, Smedsrod B, Martinez I. The liver sinusoidal endothelial cell: a cell type of controversial and confusing identity. Am J Physiol Gastrointest Liver Physiol. 2008;294(2):G391–400.
38.Xie G, Wang L, Wang X, Wang L, DeLeve LD. Isolation of periportal, midlobular, and centrilobular rat liver sinusoidal endothelial cells enables study of zonated drug toxicity. Am J Physiol Gastrointest Liver Physiol. 2010;299(5):G1204–10.
39.Geraud C, Schledzewski K, Demory A, Klein D, Kaus M, Peyre F, et al. Liver sinusoidal endothelium: a microenvironment-dependent differentiation program in rat including the novel junctional protein liver endothelial differentiation-associated protein–1. Hepatology. 2010;52(1):313–26.
40.Martinez I, Nedredal GI, Oie CI, Warren A, Johansen O, Le Couteur DG, et al. The influence of oxygen tension on the structure and function of isolated liver sinusoidal endothelial cells. Comp Hepatol. 2008;7:4.
41.Azimifar SB, Nagaraj N, Cox J, Mann M. Cell-type-resolved quantitative proteomics of murine liver. Cell Metab. 2014;20(6):1076–87.
42.Ding C, Li Y, Guo F, Jiang Y, Ying W, Li D, et al. A Cell-type-resolved Liver Proteome. Mol Cell Proteomics. 2016;15(10):3190–202.
43.Tokairin T, Nishikawa Y, Doi Y, Watanabe H, Yoshioka T, Su M, et al. A highly specific isolation of rat sinusoidal endothelial cells by the immunomagnetic bead method using SE–1 monoclonal antibody. J Hepatol. 2002;36(6):725–33.
44.Ohmura T, Enomoto K, Satoh H, Sawada N, Mori M. Establishment of a novel monoclonal antibody, SE–1, which specifically reacts with rat hepatic sinusoidal endothelial cells. J Histochem Cytochem. 1993;41(8):1253–7.
45.March S, Hui EE, Underhill GH, Khetani S, Bhatia SN. Microenvironmental regulation of the sinusoidal endothelial cell phenotype in vitro. Hepatology. 2009;50(3):920–8.
46.Yoshida M, Nishikawa Y, Omori Y, Yoshioka T, Tokairin T, McCourt P, et al. Involvement of signaling of VEGF and TGF-beta in differentiation of sinusoidal endothelial cells during culture of fetal rat liver cells. Cell Tissue Res. 2007;329(2):273–82.
47.Geraud C, Koch PS, Zierow J, Klapproth K, Busch K, Olsavszky V, et al. GATA4-dependent organ-specific endothelial differentiation controls liver development and embryonic hematopoiesis. J Clin Invest. 2017;127(3):1099–114.
48.Low TY, van Heesch S, van den Toorn H, Giansanti P, Cristobal A, Toonen P, et al. Quantitative and qualitative proteome characteristics extracted from in-depth integrated genomics and proteomics analysis. Cell Rep. 2013;5(5):1469–78.
49.Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005;102(43):15545–50.
50.Mootha VK, Lindgren CM, Eriksson KF, Subramanian A, Sihag S, Lehar J, et al. PGC–1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet. 2003;34(3):267–73.
51.Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, et al. Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet. 2000;25(1):25–9.
52.The Gene Ontology C. The Gene Ontology Resource: 20 years and still GOing strong. Nucleic Acids Res. 2019;47(D1):D330-D8.
53.Liberzon A, Birger C, Thorvaldsdóttir H, Ghandi M, Mesirov Jill P, Tamayo P. The Molecular Signatures Database Hallmark Gene Set Collection. Cell Systems. 2015;1(6):417–25.
54.Huang da W, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009;4(1):44–57.
55.Huang da W, Sherman BT, Lempicki RA. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 2009;37(1):1–13.
56.Mortazavi A, Williams BA, McCue K, Schaeffer L, Wold B. Mapping and quantifying mammalian transcriptomes by RNA-Seq. Nat Methods. 2008;5(7):621–8.
57.Malerod L, Juvet K, Gjoen T, Berg T. The expression of scavenger receptor class B, type I (SR-BI) and caveolin–1 in parenchymal and nonparenchymal liver cells. Cell Tissue Res. 2002;307(2):173–80.
58.Strauss O, Phillips A, Ruggiero K, Bartlett A, Dunbar PR. Immunofluorescence identifies distinct subsets of endothelial cells in the human liver. Sci Rep. 2017;7:44356.
59.Geraud C, Evdokimov K, Straub BK, Peitsch WK, Demory A, Dorflinger Y, et al. Unique cell type-specific junctional complexes in vascular endothelium of human and rat liver sinusoids. PLoS One. 2012;7(4):e34206.
60.Liu W, Tang L, Zhang G, Wei H, Cui Y, Guo L, et al. Characterization of a novel C-type lectin-like gene, LSECtin: demonstration of carbohydrate binding and expression in sinusoidal endothelial cells of liver and lymph node. J Biol Chem. 2004;279(18):18748–58.
61.Stutchfield BM, Antoine DJ, Mackinnon AC, Gow DJ, Bain CC, Hawley CA, et al. CSF1 Restores Innate Immunity After Liver Injury in Mice and Serum Levels Indicate Outcomes of Patients With Acute Liver Failure. Gastroenterology. 2015;149(7):1896–909 e14.
62.MacParland SA, Liu JC, Ma XZ, Innes BT, Bartczak AM, Gage BK, et al. Single cell RNA sequencing of human liver reveals distinct intrahepatic macrophage populations. Nat Commun. 2018;9(1):4383.
63.Lalor PF, Lai WK, Curbishley SM, Shetty S, Adams DH. Human hepatic sinusoidal endothelial cells can be distinguished by expression of phenotypic markers related to their specialised functions in vivo. World J Gastroenterol. 2006;12(34):5429–39.
64.Poisson J, Lemoinne S, Boulanger C, Durand F, Moreau R, Valla D, et al. Liver sinusoidal endothelial cells: Physiology and role in liver diseases. J Hepatol. 2017;66(1):212–27.
65.Li R, Oteiza A, Sorensen KK, McCourt P, Olsen R, Smedsrod B, et al. Role of liver sinusoidal endothelial cells and stabilins in elimination of oxidized low-density lipoproteins. Am J Physiol Gastrointest Liver Physiol. 2011;300(1):G71–81.
66.Mouta Carreira C, Nasser SM, di Tomaso E, Padera TP, Boucher Y, Tomarev SI, et al. LYVE–1 is not restricted to the lymph vessels: expression in normal liver blood sinusoids and down-regulation in human liver cancer and cirrhosis. Cancer Res. 2001;61(22):8079–84.
67.Ishikawa T, Yokoyama H, Matsuura T, Fujiwara Y. Fc gamma RIIb expression levels in human liver sinusoidal endothelial cells during progression of non-alcoholic fatty liver disease. PLoS One. 2019;14(1):e0211543.
68.Smedsrod B, Pertoft H, Eggertsen G, Sundstrom C. Functional and morphological characterization of cultures of Kupffer cells and liver endothelial cells prepared by means of density separation in Percoll, and selective substrate adherence. Cell Tissue Res. 1985;241(3):639–49.
69.Wang L, Wang X, Xie G, Wang L, Hill CK, DeLeve LD. Liver sinusoidal endothelial cell progenitor cells promote liver regeneration in rats. J Clin Invest. 2012;122(4):1567–73.
70.Harb R, Xie G, Lutzko C, Guo Y, Wang X, Hill CK, et al. Bone marrow progenitor cells repair rat hepatic sinusoidal endothelial cells after liver injury. Gastroenterology. 2009;137(2):704–12.
71.Oie CI, Appa RS, Hilden I, Petersen HH, Gruhler A, Smedsrod B, et al. Rat liver sinusoidal endothelial cells (LSECs) express functional low density lipoprotein receptor-related protein–1 (LRP–1). J Hepatol. 2011;55(6):1346–52.
72.Zimmermann N, Hogan SP, Mishra A, Brandt EB, Bodette TR, Pope SM, et al. Murine eotaxin–2: a constitutive eosinophil chemokine induced by allergen challenge and IL–4 overexpression. J Immunol. 2000;165(10):5839–46.
73.Miles A, Liaskou E, Eksteen B, Lalor PF, Adams DH. CCL25 and CCL28 promote alpha4 beta7-integrin-dependent adhesion of lymphocytes to MAdCAM–1 under shear flow. Am J Physiol Gastrointest Liver Physiol. 2008;294(5):G1257–67.
74.Martinez I, Sveinbjornsson B, Vidal-Vanaclocha F, Asumendi A, Smedsrod B. Differential cytokine-mediated modulation of endocytosis in rat liver endothelial cells. Biochem Biophys Res Commun. 1995;212(1):235–41.
75.Liu Y, Gardner CR, Laskin JD, Laskin DL. Classical and alternative activation of rat hepatic sinusoidal endothelial cells by inflammatory stimuli. Exp Mol Pathol. 2013;94(1):160–7.
76.Schildberg FA, Hegenbarth SI, Schumak B, Scholz K, Limmer A, Knolle PA. Liver sinusoidal endothelial cells veto CD8 T cell activation by antigen-presenting dendritic cells. Eur J Immunol. 2008;38(4):957–67.
77.Knolle PA, Gerken G. Local control of the immune response in the liver. Immunol Rev. 2000;174:21–34.
78.Onoe T, Ohdan H, Tokita D, Shishida M, Tanaka Y, Hara H, et al. Liver sinusoidal endothelial cells tolerize T cells across MHC barriers in mice. J Immunol. 2005;175(1):139–46.
79.Carambia A, Freund B, Schwinge D, Heine M, Laschtowitz A, Huber S, et al. TGF-beta-dependent induction of CD4(+)CD25(+)Foxp3(+) Tregs by liver sinusoidal endothelial cells. J Hepatol. 2014;61(3):594–9.
80.Connolly MK, Bedrosian AS, Malhotra A, Henning JR, Ibrahim J, Vera V, et al. In hepatic fibrosis, liver sinusoidal endothelial cells acquire enhanced immunogenicity. J Immunol. 2010;185(4):2200–8.
81.Smedsrod B, Pertoft H. Preparation of pure hepatocytes and reticuloendothelial cells in high yield from a single rat liver by means of Percoll centrifugation and selective adherence. J Leukoc Biol. 1985;38(2):213–30.
82.Zerbino DR, Achuthan P, Akanni W, Amode MR, Barrell D, Bhai J, et al. Ensembl 2018. Nucleic Acids Res. 2018;46(D1):D754-D61.
83.Law CW, Alhamdoosh M, Su S, Dong X, Tian L, Smyth GK, et al. RNA-seq analysis is easy as 1–2–3 with limma, Glimma and edgeR. F1000Res. 2016;5:1408.
84.Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015;43(7):e47.
85.Cox J, Mann M. MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nat Biotechnol. 2008;26(12):1367–72.
86.Schwanhausser B, Busse D, Li N, Dittmar G, Schuchhardt J, Wolf J, et al. Global quantification of mammalian gene expression control. Nature. 2011;473(7347):337–42.