The influence of oxygen tension on the structure and function of isolated liver sinusoidal endothelial cells.
The influence of oxygen tension on the structure and function of isolated liver sinusoidal endothelial cells.
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DOI：
10.1186/1476-5926-7-4
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发表时间：
2008-05-05
期刊：
影响因子：
--
通讯作者：
Smedsrød B
中科院分区：
文献类型：
--
作者：
Martinez I;Nedredal GI;Øie CI;Warren A;Johansen O;Le Couteur DG;Smedsrød B
肝窦内皮细胞（LSECs）是一种特殊的清道夫细胞，在维持肝脏和全身的稳态中起重要作用。在正常生理条件下，肝窦中遇到的氧张力通常比空气中的氧张力低得多;因此，在关于氧的更生理条件下培养新鲜分离的LSEC有望改善细胞存活、结构和功能。在这项研究中，LSECs从大鼠中分离，并在5%（常氧）或20%（高氧）氧张力下培养，并比较了几种形态功能特征。与高氧相比，在常氧下培养LSEC可改善LSEC的存活率和清道夫受体介导的内吞活性，减少促炎介质白细胞介素-6的产生，并增加抗炎细胞因子白细胞介素-10的产生。另一方面，开窗，LSECs的一个特征逐渐消失在相同的速度，无论氧张力。细胞粘附分子ICAM-1在细胞表面的表达在维持高氧的细胞中略微升高。在常氧下，内源性过氧化氢的产生急剧减少，而一氧化氮的产生没有改变。文化衰退在高氧处理的文化被废除的管理过氧化氢酶，表明在高氧环境中观察到的毒性作用主要是由内源性过氧化氢的产生。当培养物保持在更生理的氧水平下时，分离的LSEC的活力、结构和许多基本功能特征明显更好地保留。过氧化氢的内源性产生在很大程度上是在高氧环境中观察到的毒性作用的原因。
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. 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.