title: Effect of macrophage classical (M1) activation on implant-adherent macrophage interactions with Staphylococcus epidermidis: A murine in vitro model system.
abstract: A model in vitro system was developed for eliciting classical (M1) activation of surface-adherent murine macrophages, which was then used to study the interaction of the M1 macrophages with Staphylococcus epidermidis. Glass substrata were first covalently grafted with a mixture of methoxy- and biotin-terminated silanated polyethylene glycol. Interferon (IFN)-γ and/or lipopolysaccharide (LPS), ligands known to induce the highly microbicidal M1 activation state in macrophages, were biotinylated and immobilized by way of a streptavidin intermediate to the biotin-PEG base substratum. Assessment of mouse bone marrow-derived macrophage (BMDM) interleukin (IL)-12(p40) and nitric oxide response to the fabricated surfaces confirmed that the model system achieved activation of adherent macrophage: IFN-γ-presenting surfaces primed cells for M1 activation, LPS-presenting surfaces elicited innate activation, and surface presenting a combination of IFN-γ and LPS induced M1 activation. The phagocytic and microbicidal capacity of activated, surface-adherent BMDM was evaluated using S. epidermidis, a bacterial species prevalent in implant-associated infections. Results indicate that M1 activation of implant-adherent macrophages trends towards diminishing their phagocytic capacity, but enhances their microbicidal capacity for S. epidermidis.
authors.affiliation: Department of Bioengineering, University of Washington, 3720 15th Ave NE, Seattle, Washington 98195, USA.
authors.forename: Kyung R
authors.initials: KR
authors.lastname: Park
authors.forename: James D
authors.initials: JD
authors.lastname: Bryers
mesh_terms: D000818:Animals; D001710:Biotin / Q000737:chemistry / Q000494:pharmacology; D019921:Biotinylation / Q000187:drug effects; D001854:Bone Marrow Cells / Q000166:cytology; D002448:Cell Adhesion / Q000187:drug effects; D002450:Cell Communication / Q000187:drug effects; D004602:Elements; D005456:Fluorescent Dyes / Q000378:metabolism; D006801:Humans; D055767:Immobilized Proteins / Q000378:metabolism; D020007:Implants, Experimental; D007371:Interferon-gamma / Q000378:metabolism; D008024:Ligands; D008070:Lipopolysaccharides / Q000378:metabolism; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D050296:Microbial Viability / Q000187:drug effects; D023421:Models, Animal; D010587:Phagocytosis / Q000187:drug effects; D056951:Photoelectron Spectroscopy; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology; D012821:Silanes / Q000737:chemistry; D013212:Staphylococcus epidermidis / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism
chemical_list: D004602:Elements; D005456:Fluorescent Dyes; D055767:Immobilized Proteins; D008024:Ligands; D008070:Lipopolysaccharides; D012821:Silanes; D011092:Polyethylene Glycols; D001710:Biotin; D007371:Interferon-gamma