title: Shear stress and material surface effects on adherent human monocyte apoptosis.
abstract: Monocytes play a critical role as both phagocytes and mediators of inflammatory responses in the prevention of cardiovascular device-related infections. However, persistent infection of these devices still occurs and may be attributed to deleterious cellular alterations resulting from monocyte interactions with a foreign material in an environment of dynamic flow. Thus, the effects of both shear stress and adhesion to material surfaces on human monocyte apoptosis were investigated. A rotating disk system generated physiologically relevant shear stress levels (0-14 dyn/cm(2)), and shear-related apoptosis occurring in adherent monocytes was characterized. Using annexin V analysis, apoptosis of polyurethane-adherent monocytes under shear for 4 h increased to levels >70% with increasing shear in a near-linear fashion (r2 = 0.713). It was qualitatively confirmed using confocal microscopy that filamentous (F)-actin distribution was altered, that DNA fragmentation occurred, and that activated caspases were involved in shear-induced apoptosis. Static studies determined that spontaneous apoptosis was material-dependent over 72 h by demonstrating marked differences between apoptosis of monocytes adherent to a polyurethane compared to an alkyl-modified glass. Treatment with TNF-alpha augmented this material dependency in a dose-dependent fashion over time. F-actin content of TNF-alpha-treated cells decreased to <62% of untreated cells. We conclude that concomitant effects from both material surfaces and dynamic flow mediate human monocyte apoptosis and may have serious implications in the context of implanted cardiovascular device infection.
authors.affiliation: Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Shive
authors.forename: William G
authors.initials: WG
authors.lastname: Brodbeck
authors.forename: Erica
authors.initials: E
authors.lastname: Colton
authors.forename: James M
authors.initials: JM
authors.lastname: Anderson
mesh_terms: D000199:Actins / Q000737:chemistry; D017304:Annexin A5; D017209:Apoptosis / Q000502:physiology*; D001672:Biocompatible Materials; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002448:Cell Adhesion; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D020287:In Situ Nick-End Labeling; D066298:In Vitro Techniques; D008855:Microscopy, Electron, Scanning; D009000:Monocytes / Q000502:physiology*; D011140:Polyurethanes; D012212:Rheology; D015398:Signal Transduction / Q000187:drug effects; D013314:Stress, Mechanical; D013499:Surface Properties; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000199:Actins; D017304:Annexin A5; D001672:Biocompatible Materials; D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D011140:Polyurethanes; D014409:Tumor Necrosis Factor-alpha; C115016:polyetherurethane; D020169:Caspases