Department of Biomedical Engineering, College of Engineering, University of Wisconsin-Madison, WI, USA.
Biomaterials. 2012 Jan;33(1):29-37. doi: 10.1016/j.biomaterials.2011.09.044. Epub 2011 Oct 2.
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 remains 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 24 h 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.
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，并且经常在体外使用以了解对生物材料的炎症反应。以前的工作表明，在生物材料表面上原发性单核细胞附着密度急剧下降，并且随着时间的推移单核细胞的行为发生变化。然而，负责这种减少的机制仍不清楚。在这项研究中，我们探讨了主动分离和细胞死亡作为可能的调节因子。具体而言，分析了细胞外 TNF-α 和 ROS 产生作为细胞死亡的潜在内源性刺激物。发现 MMP 而不是钙蛋白酶在主动单核细胞分离中起关键作用。单核细胞死亡在 24 小时达到峰值，并且通过凋亡和坏死发生，而不是多形核白细胞死亡，主要通过凋亡发生。最后，在 TCPS 或 PEG 表面上，TNF-α 和 ROS 的产生与单核细胞死亡没有因果关系。主要单核细胞凋亡/坏死的发生以及从材料表面的主动分离不仅对体外研究具有重要意义，而且对这些细胞的体外炎症反应向体内应用的转化也具有重要意义。
