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Molecular Pathology of Liver Diseases pp 97–107Cite as

Sinusoidal Endothelial Cells

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Part of the book series: Molecular Pathology Library ((MPLB,volume 5))

Abstract

In all organs in the body, the vasculature is lined by simple, squamous epithelium, properly termed endothelium. However, the endothelia represent an extremely heterogeneous population of cells, and those of each organ, or more appropriately, each specific functional part of an organ, maintain characteristic features that enable the vasculature to perform particular roles at the blood–tissue interface [1, 2]. Regardless of the organ in question, the endothelia in normal tissues maintain a nonthrombogenically lined conduit through which a variety of blood cells and vehicle (plasma) assist in delivering oxygen, nutrients, and maintenance factors to, while removing debris, waste, and breakdown products from the underlying tissue. While the liver sinusoidal endothelium undeniably perform these duties, they possess additional phenotypes with a wide variety of unique capabilities essential to maintaining liver function.

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References

  1. Aird WC. Phenotypic heterogeneity of the endothelium: I. Structure, function, and mechanisms. Circ Res. 2007;100:158–73.

    Article  PubMed  CAS  Google Scholar 

  2. Aird WC. Phenotypic heterogeneity of the endothelium: II representative vascular beds. Circ Res. 2007;100:174–90.

    Article  PubMed  CAS  Google Scholar 

  3. Wisse E. An ultrastructural characterization of the endothelial cell in the rat liver sinusoid under normal and various experimental conditions, as a contribution to thedistinction between endothelial and Kupffer cells. J Ultrastruct Res. 1972;38:528–62.

    Article  PubMed  CAS  Google Scholar 

  4. Wisse E. An electron microscopic study of the fenestrated endothelial lining of ratliver sinusoids. J Ultrastruct Res. 1970;31:125–50.

    Article  PubMed  CAS  Google Scholar 

  5. Smedsrod B, Le Couteur D, Ikejima K, et al. Hepatic sinusoidal cells in health and disease: update from the 14th International Symposium. Liver Int. 2009;29:490–501.

    Article  PubMed  Google Scholar 

  6. Higashi N, Ueda H, Yamada O, et al. Micromorphological characteristics of hepatic sinusoidal endothelial cells and their basal laminae in five different animal species. Okajimas Folia Anat Jpn. 2002;79:135–42.

    Article  PubMed  Google Scholar 

  7. Wisse E, Jacobs F, Topal B, et al. The size of endothelialfenestrae in human liver sinusoids: implications for hepatocyte-directed gene transfer. Gene Ther. 2008;15:1193–9.

    Article  PubMed  CAS  Google Scholar 

  8. Braet F, Wisse E. Structural and functional aspects of liver sinusoidal endothelial cell fenestrae: a review. Comp Hepatol. 2002;1:1.

    Article  PubMed  Google Scholar 

  9. Wisse E, De Zanger RB, Jacobs R, McCuskey RS. Scanning electron microscopeobservations on the structure of portal veins, sinusoids and central veins in rat liver. Scan Electron Microsc. 1983;(Pt 3):1441–52.

    Google Scholar 

  10. Lautt WW, Greenway CV. Conceptual review of the hepatic vascular bed. Hepatology. 1987;7:952–63.

    Article  PubMed  CAS  Google Scholar 

  11. Viragh S, Bartok I, Papp M. The hepatic tissue spaces. Acta Med Acad Sci Hung. 1978;35:89–98.

    PubMed  CAS  Google Scholar 

  12. Lumsden AB, Henderson JM, Kutner MH. Endotoxin levels measured by achromogenic assay in portal, hepatic and peripheral venous blood in patients with cirrhosis. Hepatology. 1988;8:232–6.

    Article  PubMed  CAS  Google Scholar 

  13. Jungermann K, Kietzmann T. Oxygen: modulator of metabolic zonation and disease of the liver. Hepatology. 2000;31:255–60.

    Article  PubMed  CAS  Google Scholar 

  14. Racanelli V, Rehermann B. The liver as an immunological organ. Hepatology. 2006;43:S54–62.

    Article  PubMed  CAS  Google Scholar 

  15. Crispe IN. The liver as a lymphoid organ. Annu Rev Immunol. 2009;27:147–63.

    Article  PubMed  CAS  Google Scholar 

  16. Kmiec Z. Cooperation of liver cells in health and disease. Adv Anat Embryol Cell Biol. 2001;161:III–XIII, 1–151.

    Google Scholar 

  17. Wisse E. Ultrastructure and function of Kupffer cells and other sinusoidalcells of the liver. In: Arias JLB, Fausto N, Jakoby WB, et al., editors. The liver: biology and pathobiology. 3rd ed. New York: Raven; 1977. p. 791–818.

    Google Scholar 

  18. MacPhee PJ, Schmidt EE, Groom AC. Intermittence of blood flow in liver sinusoids, studied by high-resolution in vivo microscopy. Am J Physiol. 1995;269:G692–8.

    PubMed  CAS  Google Scholar 

  19. Braet F, Luo D, Spector I, Wisse E. Endothelial and pit cells. In: Arias JLB, Chisari FV, Fausto N, et al., editors. The liver: biology and pathobiology. 4th ed. Philadelphia: Lippincott Williams & Wilkins; 2001. p. 437–53.

    Google Scholar 

  20. Nakatani K, Kaneda K, Seki S, Nakajima Y. Pit cells as liver-associated naturalkiller cells: morphology and function. Med Electron Microsc. 2004;37:29–36.

    Article  PubMed  Google Scholar 

  21. Bouwens L, Remels L, Baekeland M, Van Bossuyt H, Wisse E. Large granular lymphocytes or “pit cells” from rat liver: isolation, ultrastructural characterization and natural killer activity. Eur J Immunol. 1987;17:37–42.

    Article  PubMed  CAS  Google Scholar 

  22. Bouwens L, Wisse E. Immuno-electron microscopic characterization of large granular lymphocytes (natural killer cells) from rat liver. Eur J Immunol. 1987;17:1423–8.

    Article  PubMed  CAS  Google Scholar 

  23. Kaneda K, Wake K. Distribution and morphological characteristics of the pit cellsin the liver of the rat. Cell Tissue Res. 1983;233:485–505.

    Article  PubMed  CAS  Google Scholar 

  24. Wisse E, Luo D, Vermijlen D, Kanellopoulou C, De Zanger R, Braet F. On thefunction of pit cells, the liver-specific natural killer cells. Semin Liver Dis. 1997;17:265–86.

    Article  PubMed  CAS  Google Scholar 

  25. Sato M, Suzuki S, Senoo H. Hepatic stellate cells: unique characteristics in cell biology and phenotype. Cell Struct Funct. 2003;28:105–12.

    Article  PubMed  CAS  Google Scholar 

  26. Li D, Friedman SL. Hepatic stellate cells: morphology, function and regulation. In: Arias IM, Boyer JL, Chisari FV, et al., editors. The liver: biology and pathobiology. 4th ed. Philadelphia: Lippincott Williams & Wilkins; 2001. p. 455–68.

    Google Scholar 

  27. Iwakiri Y, Groszmann RJ. Vascular endothelial dysfunction in cirrhosis. J Hepatol. 2007;46:927–34.

    Article  PubMed  CAS  Google Scholar 

  28. Bosch J. Vascular deterioration in cirrhosis: the big picture. J Clin Gastroenterol. 2007;41 Suppl 3:S247–53.

    Article  PubMed  Google Scholar 

  29. McCuskey RS. The hepatic microvascular system in health and its response to toxicants. Anat Rec (Hoboken). 2008;291:661–71.

    Article  Google Scholar 

  30. Ueno T, Bioulac-Sage P, Balabaud C, Rosenbaum J. Innervation of the sinusoidalwall: regulation of the sinusoidal diameter. Anat Rec A Discov Mol Cell Evol Biol. 2004;280:868–73.

    Article  PubMed  Google Scholar 

  31. Warren A, Le Couteur DG, Fraser R, et al. T lymphocytes interact with hepatocytes through fenestrations in murine liver sinusoidalendothelial cells. Hepatology. 2006;44:1182–90.

    Article  PubMed  CAS  Google Scholar 

  32. Fraser R, Dobbs BR, Rogers GW. Lipoproteins and the liver sieve: the role of thefenestrated sinusoidal endothelium in lipoprotein metabolism, atherosclerosis, and cirrhosis. Hepatology. 1995;21:863–74.

    PubMed  CAS  Google Scholar 

  33. Wisse E, De Zanger RB, Charels K, Van Der Smissen P, McCuskey RS. The liver sieve: considerations concerning the structure and function of endothelial fenestrae, thesinusoidal wall and the space of Disse. Hepatology. 1985;5:683–92.

    Article  PubMed  CAS  Google Scholar 

  34. Wack KE, Ross MA, Zegarra V, Sysko LR, Watkins SC, Stolz DB. Sinusoidal ultrastructure evaluated during the revascularization of regenerating rat liver. Hepatology. 2001;33:363–78.

    Article  PubMed  CAS  Google Scholar 

  35. Braet F. How molecular microscopy revealed new insights into the dynamics ofhepatic endothelial fenestrae in the past decade. Liver Int. 2004;24:532–9.

    Article  PubMed  Google Scholar 

  36. Oda M, Kazemoto S, Kaneko H, et al. Involvement of Ca++-calmodulin actomyosin system in contractility of hepatic sinusoidal endothelium fenestrae. In: Knook DL, Wisse E, editors. Cells of the hepatic sinusoid. Leiden: Kupffer Cell Foundation; 1993. p. 174–8.

    Google Scholar 

  37. Straub AC, Clark KA, Ross MA, et al. Arsenic-stimulated liver sinusoidal capillarization in mice requires NADPH oxidasegenerated superoxide. J Clin Invest. 2008;118:3980–9.

    Article  PubMed  CAS  Google Scholar 

  38. Gatmaitan Z, Varticovski L, Ling L, Mikkelsen R, Steffan AM, Arias IM. Studies on fenestral contraction in rat liver endothelial cells in culture. Am J Pathol. 1996;148:2027–41.

    PubMed  CAS  Google Scholar 

  39. Clavien PA. Liver regeneration: a spotlight on the novel role of platelets and serotonin. Swiss Med Wkly. 2008;138:361–70.

    PubMed  CAS  Google Scholar 

  40. Lesurtel M, Graf R, Aleil B, et al. Platelet-derived serotonin mediates liver regeneration. Science. 2006;312:104–7.

    Article  PubMed  CAS  Google Scholar 

  41. Morsiani E, Mazzoni M, Aleotti A, Gorini P, Ricci D. Increased sinusoidal wallpermeability and liver fatty change after two-thirds hepatectomy: an ultrastructural study in the rat. Hepatology. 1995;21:539–44.

    PubMed  CAS  Google Scholar 

  42. Straub AC, Stolz DB, Ross MA, et al. Arsenic stimulates sinusoidal endothelial cell capillarization and vesselremodeling in mouse liver. Hepatology. 2007;45:205–12.

    Article  PubMed  CAS  Google Scholar 

  43. Cogger VC, Muller M, Fraser R, et al. The effects of oxidative stress on the liver sieve. J Hepatol. 2004;41:370–6.

    Article  PubMed  CAS  Google Scholar 

  44. Le Couteur DG, Warren A, Cogger VC, et al. Old age and the hepatic sinusoid. Anat Rec (Hoboken). 2008;291:672–83.

    Article  Google Scholar 

  45. DeLeve LD, Wang X, Hu L, McCuskey MK, McCuskey RS. Rat liver sinusoidalendothelial cell phenotype is maintained by paracrine and autocrine regulation. Am J Physiol Gastrointest Liver Physiol. 2004;287:G757–63.

    Article  PubMed  CAS  Google Scholar 

  46. DeLeve LD, Wang X, McCuskey MK, McCuskey RS. Rat liver endothelial cellsisolated by anti-CD31 immunomagnetic separation lack fenestrae and sieve plates. Am J Physiol Gastrointest Liver Physiol. 2006;291:G1187–9.

    Article  PubMed  CAS  Google Scholar 

  47. Ogi M, Yokomori H, Oda M, et al. Distribution and localization of caveolin-1 in sinusoidal cells in rat liver. Med Electron Microsc. 2003;36:33–40.

    Article  PubMed  CAS  Google Scholar 

  48. Warren A, Cogger VC, Arias IM, McCuskey RS, Lec DG. Liver sinusoidalendothelial fenestrations in caveolin-1 knockout mice. Microcirculation. 2010;17:32–8.

    Article  PubMed  CAS  Google Scholar 

  49. Elvevold K, Smedsrod B, Martinez I. The liver sinusoidal endothelial cell: a celltype of controversial and confusing identity. Am J Physiol Gastrointest Liver Physiol. 2008;294:G391–400.

    Article  PubMed  CAS  Google Scholar 

  50. Shiratori Y, Tananka M, Kawase T, Shiina S, Komatsu Y, Omata M. Quantification of sinusoidal cell function in vivo. Semin Liver Dis. 1993;13:39–49.

    Article  PubMed  CAS  Google Scholar 

  51. Seternes T, Sorensen K, Smedsrod B. Scavenger endothelial cells of vertebrates: anonperipheral leukocyte system for high-capacity elimination of waste macromolecules. Proc Natl Acad Sci U S A. 2002;99:7594–7.

    Article  PubMed  CAS  Google Scholar 

  52. Knolle PA, Limmer A. Control of immune responses by savenger liver endothelial cells. Swiss Med Wkly. 2003;133:501–6.

    PubMed  CAS  Google Scholar 

  53. Knolle PA, Germann T, Treichel U, et al. Endotoxin down-regulates T cell activation by antigen-presenting liver sinusoidal endothelial cells. J Immunol. 1999;162:1401–7.

    PubMed  CAS  Google Scholar 

  54. Berg M, Wingender G, Djandji D, et al. Cross-presentation of antigens from apoptotic tumor cells by liver sinusoidal endothelial cells leads to tumor-specific CD8+ T cell tolerance. Eur J Immunol. 2006;36:2960–70.

    Article  PubMed  CAS  Google Scholar 

  55. Limmer A, Ohl J, Wingender G, et al. Cross-presentation of oral antigens by liver sinusoidal endothelial cells leads to CD8 Tcell tolerance. Eur J Immunol. 2005;35:2970–81.

    Article  PubMed  CAS  Google Scholar 

  56. Tokita D, Shishida M, Ohdan H, et al. Liver sinusoidal endothelial cells that endocytose allogeneic cells suppress T cells with indirect allospecificity. J Immunol. 2006;177:3615–24.

    PubMed  CAS  Google Scholar 

  57. 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;38:957–67.

    Article  PubMed  CAS  Google Scholar 

  58. DeLeve LD. Hepatic microvasculature in liver injury. Semin Liver Dis. 2007;27:390–400.

    Article  PubMed  CAS  Google Scholar 

  59. DeLeve LD, Valla DC, Garcia-Tsao G. Vascular disorders of the liver. Hepatology. 2009;49:1729–64.

    Article  PubMed  CAS  Google Scholar 

  60. Xu B, Broome U, Uzunel M, Nava S, et al. Capillarization of hepatic sinusoid by liver endothelial cell-reactive autoantibodies in patients with cirrhosis and chronic hepatitis. Am J Pathol. 2003;163:1275–89.

    Article  PubMed  CAS  Google Scholar 

  61. Harb R, Xie G, Lutzko C, et al. Bonemarrow progenitor cells repair rat hepatic sinusoidal endothelial cells after liver injury. Gastroenter ology. 2009;137:704–12.

    Article  PubMed  Google Scholar 

  62. Myagkaya GL, van Veen HA, James J. Ultrastructural changes in the rat liver during Euro-Collins storage, compared with hypothermic in vitro ischemia. Virchows Arch B Cell Pathol Incl Mol Pathol. 1987;53:176–82.

    Article  PubMed  CAS  Google Scholar 

  63. Caldwell-Kenkel JC, Currin RT, Tanaka Y, Thurman RG, Lemasters JJ. Kupffer cell activation and endothelial cell damage after storage of rat livers: effects ofreperfusion. Hepatology. 1991;13:83–95.

    PubMed  CAS  Google Scholar 

  64. Clavien PA. Sinusoidal endothelial cell injury during hepatic preservation and reperfusion. Hepatology. 1998;28:281–5.

    Article  PubMed  CAS  Google Scholar 

  65. Stolz DB, Ross MA, Ikeda A, Tomiyama K, Kaizu T, Geller DA, et al. Sinusoidal endothelial cell repopulation following ischemia/reperfusion injury in rat liver transplantation. Hepatology. 2007;46:1464–75.

    Article  PubMed  CAS  Google Scholar 

  66. Fujii H, Hirose T, Oe S, et al. Contribution of bone marrow cells to liver regeneration after partial hepatectomy in mice. J Hepatol. 2002;36:653–9.

    Article  PubMed  CAS  Google Scholar 

  67. Seglen PO. Preparation of isolated rat liver cells. Methods Cell Biol. 1976;13:2983.

    Google Scholar 

  68. Braet F, De Zanger R, Sasaoki T, et al. Assessment of a method of isolation, purification, and cultivation of rat liver sinusoidal endothelial cells. Lab Invest. 1994;70:944–52.

    PubMed  CAS  Google Scholar 

  69. Eyhorn S, Schlayer HJ, Henninger HP, et al. Rat hepatic sinusoidal endothelial cells in monolayer culture. Biochemical and ultrastructural characteristics. J Hepatol. 1988;6:23–35.

    Article  PubMed  CAS  Google Scholar 

  70. Knook DL, Sleyster EC. Separation of Kupffer and endothelial cells of the ratliver by centrifugal elutriation. Exp Cell Res. 1976;99:444–9.

    Article  PubMed  CAS  Google Scholar 

  71. Tokairin T, Nishikawa Y, Doi Y, et al. A highly specific isolation of rat sinusoidal endothelial cells by the immunomagnetic bead method using SE-1 monoclonal antibody. J Hepatol. 2002;36:725–33.

    Article  PubMed  CAS  Google Scholar 

  72. Enomoto K, Nishikawa Y, Omori Y, et al. Cell biology and pathology of liver sinusoidal endothelial cells. Med Electron Microsc. 2004;37:208–15.

    Article  PubMed  Google Scholar 

  73. March S, Hui EE, Underhill GH, Khetani S, Bhatia SN. Microenvironmental regulation of the sinusoidal endothelial cell phenotype in vitro. Hepatology. 2009;50:920–8.

    Article  PubMed  CAS  Google Scholar 

  74. Onoe T, Ohdan H, Tokita D, et al. Liver sinusoidal endothelial cells tolerize T cells across MHC barriers in mice. J Immunol. 2005;175:139–46.

    PubMed  CAS  Google Scholar 

  75. Hansen B, Longati P, Elvevold K, et al. Stabilin-1 and stabilin-2 are both directed into the early endocyticpathway in hepatic sinusoidal endothelium via interactions with clathrin/AP-2, independent of ligand binding. Exp Cell Res. 2005;303:160–73.

    Article  PubMed  CAS  Google Scholar 

  76. 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;61:8079–84.

    PubMed  CAS  Google Scholar 

  77. Stolz DB, Ross MA, Salem HM, Mars WM, Michalopoulos GK, Enomoto K. Cationic colloidal silica membrane perturbation as a means of examining changes at thesinusoidal surface during liver regeneration. Am J Pathol. 1999;155:1487–98.

    Article  PubMed  CAS  Google Scholar 

  78. Ross MA, Sander CM, Kleeb TB, Watkins SC, Stolz DB. Spatiotemporalexpression of angiogenesis growth factor receptors during the revascularization ofregenerating rat liver. Hepatology. 2001;34:1135–48.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The author acknowledges the amazing technical assistance of the entire staff of the Center for Biologic Imaging, at the University of Pittsburgh Medical School, but especially Mark Ross for his dedication to all aspects of liver processing and imaging. Supported by NIH grant R01 CA76541 to DBS.

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  1. Department of Cell Biology and Physiology, University of Pittsburgh, Pittsburgh, PA, USA

    Donna Beer Stolz

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  1. Donna Beer Stolz
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Correspondence to Donna Beer Stolz .

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  1. School of Medicine, Dept. Pathology, University of Pittsburgh, 200 Lothrop Street, S421-BST, Pittsburgh, 15261, Pennsylvania, USA

    Satdarshan P. S. Monga

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Stolz, D.B. (2011). Sinusoidal Endothelial Cells. In: Monga, S. (eds) Molecular Pathology of Liver Diseases. Molecular Pathology Library, vol 5. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-7107-4_7

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  • DOI: https://doi.org/10.1007/978-1-4419-7107-4_7

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