title: The effects of phorbol ester activation and reactive oxygen species scavengers on the macrophage-mediated foreign body reaction to polyurethanes.
abstract: Phorbol myristate acetate, a protein kinase C activator, inhibited monocyte-derived macrophage (MDM)-mediated degradation of aliphatic (HDI) polycarbonate-based polyurethanes but not degradation of the aromatic polycarbonate-based polyurethane (MDI). The objectives of this study were to determine if reactive oxygen species are involved in the phorbol myristate acetate effect on esterase activity and MDM-mediated polycarbonate-based polyurethane degradation and to find a good marker of material-initiated activation of MDM. The phorbol myristate acetate-dependent effects of the material chemistry on cell activation and degradation were evaluated by adding reactive oxygen species scavengers, catalase plus superoxide dismutase to MDM and assaying possible markers of MDM activation: esterase activity, acid phosphatase activity, and high molecular weight group box 1 protein (HMGB1). All treatments reduced the esterase activity in MDM on HDI but not in MDM on MDI. Acid phosphatase was inhibited in MDM to varying degrees on all surfaces by phorbol myristate acetate or catalase plus superoxide dismutase either alone or together. Secretion of HMGB1 from MDM on HDI431 was higher than MDI; however only secretion from MDM on HDI was inhibited by phorbol myristate acetate. In MDM on HDI, catalase plus superoxide dismutase reduced intracellular HMGB1 levels +/- phorbol myristate acetate; whereas, catalase, superoxide dismutase plus phorbol myristate acetate increased intracellular HMGB1 in MDM on MDI, suggesting that esterase and HMGB1 are more specific markers of activation than acid phosphatase. Manipulation of signaling pathways may provide insight surrounding the mechanism of activation for oxidative and/or hydrolytic degradative pathways in the MDM response to material surface chemistry.
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Joanne E
authors.initials: JE
authors.lastname: McBane
authors.forename: Loren A
authors.initials: LA
authors.lastname: Matheson
authors.forename: J Paul
authors.initials: JP
authors.lastname: Santerre
authors.forename: Rosalind S
authors.initials: RS
authors.lastname: Labow
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005549:Foreign-Body Reaction / Q000139:chemically induced / Q000276:immunology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D024243:HMGB1 Protein / Q000378:metabolism; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology*; D008954:Models, Biological; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D011076:Polycarboxylate Cement / Q000494:pharmacology; D011140:Polyurethanes / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013499:Surface Properties / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
chemical_list: D016166:Free Radical Scavengers; D024243:HMGB1 Protein; D011076:Polycarboxylate Cement; D011140:Polyurethanes; D017382:Reactive Oxygen Species; C005506:polycarbonate; D011493:Protein Kinase C; D000135:Acid Phosphatase; D013755:Tetradecanoylphorbol Acetate