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

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.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.The liver sinusoids are lined by endothelial cells that have a unique structure and function essential for hepatic and systemic homeostasis. Much of our understanding of the biology of the LSECs has been generated in experiments curried out on cultured LSECs, mostly derived from rodents. However, in vitro preservation of functionally intact LSECs during isolation and culture has been a challenge because isolated LSECs have poor viability and rapidly loose many of their functional and morphological characteristics [1,2]. Some improvements have been achieved with autologous serum [3], hepatocyte-conditioned medium [2], VEGF or sophisticated synthetic serum-free medium [4].Traditionally, most of the cell cultivation of today is performe