Encyclopedia of Medical Immunology

2014 Edition
| Editors: Ian R. Mackay, Noel R. Rose, Betty Diamond, Anne Davidson

Ultrastructure of the Liver Sinusoid

  • David G. Le CouteurEmail author
  • Alessandra Warren
  • Victoria Cogger
  • Patrick Bertolino
Reference work entry
DOI: https://doi.org/10.1007/978-0-387-84828-0_71

The Liver Sinusoid

The liver sinusoids are the blood vessels that make up the microcirculation of the liver. Ultrastructure refers to the morphological cellular features that can be resolved by electron microscopy.

The liver has many immunological roles including production of acute-phase proteins, clearance of waste products generated by systemic inflammation and immune responses, deletion of activated T cells, and induction of tolerance to ingested and self-antigens (Parker and Picut 2012). The liver sinusoids form the interface between circulating blood and the hepatocytes thus are strategically placed to undertake and/or regulate the immune functions of the liver.

The sinusoidal vessels branch off from the terminal portal venules, carry blood between the plates of hepatocytes, and then drain into the central venules (Fig. 1). Each sinusoid traverses a distance of about 1 mm, and there are about one billion sinusoids in a human liver (Fraser et al. 2012). They occupy about 30 % of...
This is a preview of subscription content, log in to check access.


  1. Arii S, Imamura M. Physiological role of sinusoidal endothelial cells and Kupffer cells and their implication in the pathogenesis of liver injury. J Hepatobiliary Pancreat Surg. 2000;7:40–8.PubMedCrossRefGoogle Scholar
  2. Bertolino P. Impaired function of dendritic cells translocating the liver sinusoids: a veto effect contributing to intrahepatic tolerance? Eur J Immunol. 2008;38:938–41.PubMedCrossRefGoogle Scholar
  3. Cogger VC, Le Couteur DG. Fenestrations in the liver sinusoidal endothelial cell. In: Arias I, Wolkoff A, Boyer J, Shafritz D, Fausto N, Alter H, Cohen A, editors. The liver: biology and pathobiology. Hokoben: Wiley; 2009. p. 387–404.Google Scholar
  4. Cogger VC, Muller M, Fraser R, McLean AJ, Khan J, Le Couteur DG. The effects of oxidative stress on the liver sieve. J Hepatol. 2004;41:370–6.PubMedCrossRefGoogle Scholar
  5. Cogger VC, McNerney GP, Nyunt T, Deleve LD, McCourt P, Smedsrod B, et al. Three-dimensional structured illumination microscopy of liver sinusoidal endothelial cell fenestrations. J Struct Biol. 2010;171:382–8.PubMedCrossRefPubMedCentralGoogle Scholar
  6. Fraser R, Cogger VC, Dobbs B, Jamieson HA, Warren A, Hilmer SN, et al. The liver sieve and atherosclerosis. Pathology. 2012;44:181–6.PubMedCrossRefGoogle Scholar
  7. Hilmer SN, Cogger VC, Le Couteur DG. Basal activity of Kupffer cells increases with old age. J Gerontol A Biol Sci Med Sci. 2007;62:973–8.PubMedCrossRefGoogle Scholar
  8. Holz LE, Warren A, Le Couteur DG, Bowen DG, Bertolino P. CD8+ T cell tolerance following antigen recognition on hepatocytes. J Autoimmun. 2010;34:15–22.PubMedCrossRefGoogle Scholar
  9. Le Couteur DG, Fraser R, Cogger VC, McLean AJ. Hepatic pseudocapillarisation and atherosclerosis in ageing. Lancet. 2002;359:1612–5.PubMedCrossRefGoogle Scholar
  10. Le Couteur DG, Fraser R, Hilmer S, Rivory LP, McLean AJ. The hepatic sinusoid in aging and cirrhosis – effects on hepatic substrate disposition and drug clearance. Clin Pharmacokinet. 2005;44:187–200.PubMedCrossRefGoogle Scholar
  11. Naito M, Hasegawa G, Ebe Y, Yamamoto T. Differentiation and function of Kupffer cells. Med Electron Microsc. 2004;37:16–28.PubMedCrossRefGoogle Scholar
  12. Nakatani K, Kaneda K, Seki S, Nakajima Y. Pit cells as liver-associated natural killer cells: morphology and function. Med Electron Microsc. 2004;37:29–36.PubMedCrossRefGoogle Scholar
  13. Parker GA, Picut CA. Immune functioning in non lymphoid organs: the liver. Toxicol Pathol. 2012;40:237–47.PubMedCrossRefGoogle Scholar
  14. Senoo H. Structure and function of hepatic stellate cells. Med Electron Microsc. 2004;37:3–15.PubMedCrossRefGoogle Scholar
  15. Senoo H, Kojima N, Sato M. Vitamin A-storing cells (stellate cells). Vitam Horm. 2007;75:131–59.PubMedCrossRefGoogle Scholar
  16. Sørensen 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. 2012;303:R1217.Google Scholar
  17. Warren A, Le Couteur DG, Fraser R, Bowen DG, McCaughan GW, Bertolino P. T lymphocytes interact with hepatocytes through fenestrations in murine liver sinusoidal endothelial cells. Hepatology. 2006;44:1182–90.PubMedCrossRefGoogle Scholar
  18. Warren A, Bertolino P, Benseler V, Fraser R, McCaughan GW, Le Couteur DG. Marked changes of the hepatic sinusoid in a transgenic mouse model of acute immune-mediated hepatitis. J Hepatol. 2007;46:239–46.PubMedCrossRefGoogle Scholar
  19. Warren A, Chaberek S, Ostrowski K, Cogger VC, Hilmer SN, McCuskey RS, et al. Effects of old age on vascular complexity and dispersion of the hepatic sinusoidal network. Microcirculation. 2008;15:191–202.PubMedCrossRefPubMedCentralGoogle Scholar
  20. Warren A, Cogger VC, Fraser R, Deleve LD, McCuskey RS, Le Couteur DG. The effects of old age on hepatic stellate cells. Curr Gerontol Geriatr Res. 2011;2011:439835.PubMedCrossRefPubMedCentralGoogle Scholar
  21. Wisse W, De Zanger RB, Charels K, Van Der Smissen P, McCuskey RS. The liver sieve: considerations concerning the structure and function of endothelial fenestrae, the sinusoidal wall and the space of Disse. Hepatology. 1985;5:683–92.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • David G. Le Couteur
    • 1
    Email author
  • Alessandra Warren
    • 1
  • Victoria Cogger
    • 1
  • Patrick Bertolino
    • 2
  1. 1.Centre for Education and Research on Ageing (CERA), and the ANZAC Medical Research InstituteUniversity of SydneySydneyAustralia
  2. 2.Liver Immunology group, Centenary Institute & AW Morrow Gastroenterology and Liver CentreUniversity of SydneySydneyAustralia