Department of Chemical Engineering, University of Michigan, Ann Arbor, Michigan, United States of America.
PLoS One. 2012;7(2):e31874. doi: 10.1371/journal.pone.0031874. Epub 2012 Feb 24.
Endothelial cells (ECs) are continuously exposed to hemodynamic forces imparted by blood flow. While it is known that endothelial behavior can be influenced by cytokine activation or fluid shear, the combined effects of these two independent agonists have yet to be fully elucidated.
We investigated EC response to long-term inflammatory cues under physiologically relevant shear conditions via E-selectin expression where monolayers of human umbilical vein ECs were simultaneously exposed to laminar fluid shear and interleukin-1ß (shear-cytokine activation) in a parallel plate flow chamber.
Naïve ECs exposed to shear-cytokine activation display significantly higher E-selectin expression for up to 24 hr relative to ECs activated in static (static-cytokine). Peak E-selectin expression occurred after 8-12 hr of continuous shear-cytokine activation contrary to the commonly observed 4-6 hr peak expression in ECs exposed to static-cytokine activation. Cells with some history of high shear conditioning exhibited either high or muted E-selectin expression depending on the durations of the shear pre-conditioning and the ensuing shear-cytokine activation. Overall, the presented data suggest that a high laminar shear enhances acute EC response to interleukin-1ß in naïve or shear-conditioned ECs as may be found in the pathological setting of ischemia/reperfusion injury while conferring rapid E-selectin downregulation to protect against chronic inflammation.
内皮细胞（ECs）持续暴露于血流施加的血液动力。虽然已知内皮细胞行为可受细胞因子激活或流体剪切的影响，但这两种独立激动剂的联合作用尚未完全阐明。
我们通过 E-选择素表达研究了在生理相关剪切条件下内皮细胞对长期炎症信号的反应，其中单层人脐静脉内皮细胞同时在平行板流动室中暴露于层流剪切和白细胞介素-1β（剪切-细胞因子激活）。
与在静态（静态-细胞因子）中激活的 EC 相比，暴露于剪切-细胞因子激活的 naive EC 显示出高达 24 小时的显著更高的 E-选择素表达。与在静态细胞因子激活中观察到的 4-6 小时的常见高峰表达相反，连续剪切-细胞因子激活 8-12 小时后出现了 E-选择素表达的高峰。具有高剪切预处理历史的细胞根据剪切预处理的持续时间和随后的剪切-细胞因子激活，表现出高或低的 E-选择素表达。总体而言，所呈现的数据表明，高层流剪切增强了对缺血/再灌注损伤等病理状态下的新生或剪切条件的 EC 对白细胞介素-1β的急性反应，同时迅速下调 E-选择素以防止慢性炎症。
