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

机译:氧分压对离体肝窦内皮细胞结构和功能的影响

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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.
机译:背景肝窦内皮细胞(LSEC)是专门的清道夫细胞,在维持肝和全身稳态方面起着至关重要的作用。在正常的生理条件下,肝正弦曲线中遇到的氧气压力通常大大低于空气中的氧气压力。因此,就氧气而言,在更生理的条件下培养新鲜分离的LSEC有望改善细胞存活率,结构和功能。在这项研究中,从大鼠中分离出LSEC,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。结果高氧条件下培养LSEC,而不是高氧,可提高LSEC的存活率和清道夫受体介导的内吞活性,减少促炎介质,白介素6的产生,并增加抗炎细胞因子白介素-2的产生。 10。另一方面,与氧气张力无关,开窗是LSECs的特征,以相同的速率逐渐消失。高氧维持的细胞中细胞粘附分子ICAM-1的表达在细胞表面稍高。在常氧下,过氧化氢的内源性产生大大减少,而一氧化氮的产生却没有改变。通过使用过氧化氢酶可以消除经高氧处理的培养物中的培养物下降,这表明在高氧环境中观察到的毒性作用很大程度上是由过氧化氢的内源性产生的。结论当将培养物维持在较高的生理氧水平下时,分离的LSEC的活力,结构和许多基本功能特性可以得到更好的保存。过氧化氢的内生产生在很大程度上负责在高氧环境中观察到的毒性作用。

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