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The Internalization Time Course of a Given Lipopolysaccharide Chemotype Does Not Correspond to Its Activation Kinetics in Monocytes

机译:给定的脂多糖化学型的内在化时间过程不与其在单核细胞中的活化动力学相对应

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The prerequisites for the initiation of pathophysiological effects of endotoxin (lipopolysaccharide [LPS]) include binding to and possibly internalization by target cells. Monocytes/macrophages are prominent target cells which are activated by LPS to release various pro- and anti-inflammatory mediators. The aim of the present study was to establish a new method to determine the binding and internalization rate of different LPS chemotypes by human monocytes and to correlate these phenomena with biological activity. It was found that membrane-bound LPS disappears within hours from the surface being internalized into the cell. Further, a correlation between the kinetics of internalization and the length of the sugar chain as well as an inverse correlation between the time course of internalization and LPS hydrophobicity was revealed. Comparison of the internalization kinetics of different LPS chemotypes with kinetics of tumor necrosis factor alpha release and kinetics of oxidative burst did not reveal any correlation of these parameters. These findings suggest that cellular internalization of and activation by LPS are mechanisms which are independently regulated.
机译:启动内毒素(脂多糖[LPS])的病理生理作用的先决条件包括与靶细胞结合并可能被其内在化。单核细胞/巨噬细胞是突出的靶细胞,其被LPS激活以释放各种促炎和抗炎介质。本研究的目的是建立一种新的方法,以确定人单核细胞对不同LPS化学型的结合和内在化速率,并将这些现象与生物学活性相关联。发现与膜结合的LPS在被内化进入细胞的表面后数小时内消失。此外,揭示了内在化动力学和糖链长度之间的相关性以及内在化的时间过程和LPS疏水性之间的反相关性。比较不同LPS化学型的内在动力学与肿瘤坏死因子α释放动力学和氧化爆发动力学的比较,没有发现这些参数之间存在任何相关性。这些发现表明,LPS的细胞内在化和激活是独立调节的机制。

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