title: Active leukocyte detachment and apoptosis/necrosis on PEG hydrogels and the implication in the host inflammatory response.
abstract: 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.
authors.affiliation: Department of Biomedical Engineering, College of Engineering, University of Wisconsin-Madison, WI, USA. hmwaldeck@wisc.edu
authors.forename: Heather
authors.initials: H
authors.lastname: Waldeck
authors.forename: Xintong
authors.initials: X
authors.lastname: Wang
authors.forename: Evan
authors.initials: E
authors.lastname: Joyce
authors.forename: Weiyuan John
authors.initials: WJ
authors.lastname: Kao
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000235:genetics*; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D020100:Hydrogels / Q000737:chemistry* / Q000494:pharmacology*; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects*; D009336:Necrosis / Q000139:chemically induced*; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D011092:Polyethylene Glycols / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D020100:Hydrogels; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D011092:Polyethylene Glycols