Active leukocyte detachment and apoptosis/necrosis on PEG hydrogels and the implication in the host inflammatory response.
Active leukocyte detachment and apoptosis/necrosis on PEG hydrogels and the implication in the host inflammatory response.
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DOI：
10.1016/j.biomaterials.2011.09.044
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发表时间：
2012-01
期刊：
影响因子：
14
通讯作者：
Kao, Weiyuan John
中科院分区：
文献类型：
--
作者：
Waldeck, Heather;Wang, Xintong;Joyce, Evan;Kao, Weiyuan John
单核细胞/巨噬细胞长期以来一直被认为是炎症和伤口愈合的关键参与者，并且经常在体外用于了解生物材料的炎症反应。先前的工作已经证明，随着时间的推移，原代单核细胞粘附在生物材料表面的密度急剧下降，同时单核细胞的行为也发生了变化。然而，造成这种减少的机制尚不清楚。在这项研究中，我们探讨了主动脱离和细胞死亡作为可能的调节因素。具体来说，细胞外TNF-α和ROS的产生被分析为细胞死亡的潜在内源性刺激物。发现MMPs，而不是calpain，在活跃的单核细胞脱离中起关键作用。单核细胞死亡在24小时达到高峰，以凋亡和坏死两种方式发生，而多形核白细胞主要通过凋亡发生死亡。最后，TNF-α和ROS的产生与TCPS或PEG表面的单核细胞死亡没有因果关系。原发性单核细胞凋亡/坏死的发生以及从物质表面的主动脱离不仅在体外研究中有意义，而且在这些细胞的体外炎症反应转化为体内应用中也有意义。
Monocytes/Macrophages have long been recognized as key players in inflammation and wound healing and are often employed in vitro to gain an understanding of the inflammatory response to biomaterials. Previous work has demonstrated a drastic decrease in primary monocyte adherent density on biomaterial surfaces coupled with a change in monocyte behavior over time. However, the mechanism responsible for this decrease was unclear. In this study, we explored active detachment and cellular death as possible regulating factors. Specifically, extracellular TNF-α and ROS production were analyzed as potential endogenous stimulators of cell death. MMPs, but not calpains, were found to play a key role in active monocyte detachment. Monocyte death was found to peak at 24hr and occur by both apoptosis and necrosis as opposed to polymorphonuclear leukocyte death which mainly occurred through apoptosis. Finally, TNF-α and ROS production were not found to have a causal relationship with monocyte death on TCPS or PEG surfaces. The occurrence of primary monocyte apoptosis/necrosis as well as active detachment from a material surface has implications not only in in vitro study, but also in the translation of the in vitro inflammatory response of these cells to in vivo applications.
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影响因子：
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