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The influence of oxygen tension on the structure and function of isolated liver sinusoidal endothelial cells

Inigo Martinez1*, Geir I Nedredal2, Cristina I Øie1, Alessandra Warren3, Oddmund Johansen1, David G Le Couteur3 and Bård Smedsrød1

Author Affiliations

1 Department of Cell Biology and Histology, IMB, Department of Medicine, IKM, Department of Orthopaedic Surgery, IKM, University of Tromsø, Norway

2 Surgical Research Lab, IKM, University of Tromsø, Norway

3 Centre for Education and Research on Ageing and the ANZAC Research Institute, Concord RG Hospital and University of Sydney, Australia

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Comparative Hepatology 2008, 7:4  doi:10.1186/1476-5926-7-4

Published: 5 May 2008

Abstract

Background

Liver sinusoidal endothelial cells (LSECs) are specialized scavenger cells, with crucial roles in maintaining hepatic and systemic homeostasis. Under normal physiological conditions, the oxygen tension encountered in the hepatic sinusoids is in general considerably lower than the oxygen tension in the air; therefore, cultivation of freshly isolated LSECs under more physiologic conditions with regard to oxygen would expect to improve cell survival, structure and function. In this study LSECs were isolated from rats and cultured under either 5% (normoxic) or 20% (hyperoxic) oxygen tensions, and several morpho-functional features were compared.

Results

Cultivation of LSECs under normoxia, as opposed to hyperoxia improved the survival of LSECs and scavenger receptor-mediated endocytic activity, reduced the production of the pro-inflammatory mediator, interleukin-6 and increased the production of the anti-inflammatory cytokine, interleukin-10. On the other hand, fenestration, a characteristic feature of LSECs disappeared gradually at the same rate regardless of the oxygen tension. Expression of the cell-adhesion molecule, ICAM-1 at the cell surface was slightly more elevated in cells maintained at hyperoxia. Under normoxia, endogenous generation of hydrogen peroxide was drastically reduced whereas the production of nitric oxide was unaltered. Culture decline in high oxygen-treated cultures was abrogated by administration of catalase, indicating that the toxic effects observed in high oxygen environments is largely caused by endogenous production of hydrogen peroxide.

Conclusion

Viability, structure and many of the essential functional characteristics of isolated LSECs are clearly better preserved when the cultures are maintained under more physiologic oxygen levels. Endogenous production of hydrogen peroxide is to a large extent responsible for the toxic effects observed in high oxygen environments.