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细胞因子与环境相关颗粒的差异结合:体外实验结果误判的一个可能原因?

Differential binding of cytokines to environmentally relevant particles: a possible source for misinterpretation of in vitro results?

作者信息

Kocbach A, Totlandsdal A I, Låg M, Refsnes M, Schwarze P E

机构信息

Division of Environmental Medicine, Norwegian Institute of Public Health, P.O. Box 4404 Nydalen, 0403 Oslo, Norway.

出版信息

Toxicol Lett. 2008 Jan 30;176(2):131-7. doi: 10.1016/j.toxlet.2007.10.014. Epub 2007 Nov 7.

DOI:10.1016/j.toxlet.2007.10.014
PMID:18079072
Abstract

Inflammation is considered as a key event in adverse health effects associated with exposure to ambient particulate matter. The inflammatory potential of particles is often compared using in vitro cell systems, where the particle-induced release of pro-inflammatory cytokines is measured. A major concern in these assays is the potential of particles to bind cytokines, which may lead to an underestimation of the inflammatory potential. We therefore investigated the cytokine binding to a selection of particle samples, including particles collected from outdoor sources (wood combustion, traffic) and particles commonly used to model environmental sources (ultrafine carbon black, diesel, quartz), for a range of pro-inflammatory cytokines (TNF-alpha, IL-1beta, IL-6, IL-8). Furthermore, the influence of serum proteins and particle- and cytokine concentrations on the cytokine binding was studied. Cytokines primarily bound to carbonaceous particles (up to 85%), not to mineral particles. Furthermore, depending on the type of cytokine, the cytokine binding could be reduced partly or completely by adding serum proteins to the cell growth medium or particle suspensions. Based on these observations we recommend either to adjust culturing and exposure conditions to prevent cytokine binding, or to adjust the measured cytokine release by application of correction factors obtained from cytokine binding experiments.

摘要

炎症被认为是与暴露于环境颗粒物相关的不良健康影响中的关键事件。通常使用体外细胞系统比较颗粒物的炎症潜力,在该系统中测量颗粒物诱导的促炎细胞因子释放。这些检测中的一个主要问题是颗粒物结合细胞因子的可能性,这可能导致对炎症潜力的低估。因此,我们研究了一系列促炎细胞因子(肿瘤坏死因子-α、白细胞介素-1β、白细胞介素-6、白细胞介素-8)与一系列颗粒物样本的结合情况,这些样本包括从室外来源(木材燃烧、交通)收集的颗粒物以及常用于模拟环境来源的颗粒物(超细炭黑、柴油、石英)。此外,还研究了血清蛋白以及颗粒物和细胞因子浓度对细胞因子结合的影响。细胞因子主要与碳质颗粒物结合(高达85%),而不与矿物颗粒物结合。此外,根据细胞因子的类型,通过向细胞生长培养基或颗粒物悬浮液中添加血清蛋白,细胞因子结合可部分或完全降低。基于这些观察结果,我们建议要么调整培养和暴露条件以防止细胞因子结合,要么通过应用从细胞因子结合实验获得的校正因子来调整测量的细胞因子释放量。

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