title: Effects of delayed delivery of dexamethasone-21-phosphate via subcutaneous microdialysis implants on macrophage activation in rats.
abstract: Macrophage activation is of interest in the biomaterials field since macrophages with an M(Dex) characteristic phenotype, i.e., CD68(+)CD163(+), are believed to result in improved integration of the biomaterial as well as improved tissue remodeling and increased biomaterial longevity. To facilitate delivery of a macrophage modulator, dexamethasone-21-phosphate (Dex), microdialysis probes were subcutaneously implanted in male Sprague-Dawley rats. Dex localized delivery was delayed to the third day post implantation as a means to alter macrophage activation state at an implant site. To better elucidate the molecular mechanisms associated with M(Dex) macrophage activation, CCL2 was quantified in dialysates, gene expression ratios were determined from excised tissue surrounding the implant, histological analyses, and immunohistochemical analyses (CD68, CD163) were performed. Delayed Dex infusion resulted in the up-regulation of IL-6 at the transcript level in the tissue in contact with the microdialysis probe and decreased CCL2 concentrations collected in dialysates. Histological analyses showed increased cellular density as compared to controls in response to delayed Dex infusion. Dex delayed infusion resulted in an increased percentage of CD68(+)CD163(+), M(Dex), macrophages in the tissue surrounding the microdialysis probe as compared to probes that served as controls.
authors.affiliation: Cell and Molecular Biology Program, University of Arkansas, Fayetteville, AR 72701, USA; Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, AR 72701, USA.
authors.forename: Geoffrey D
authors.initials: GD
authors.lastname: Keeler
authors.affiliation: Cell and Molecular Biology Program, University of Arkansas, Fayetteville, AR 72701, USA; Department of Biological Sciences, University of Arkansas, Fayetteville, AR 72701, USA.
authors.forename: Jeannine M
authors.initials: JM
authors.lastname: Durdik
authors.affiliation: Cell and Molecular Biology Program, University of Arkansas, Fayetteville, AR 72701, USA; Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, AR 72701, USA. Electronic address: jstenken@uark.edu.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Stenken
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology; D018932:Chemokine CCL2 / Q000276:immunology*; D016207:Cytokines / Q000276:immunology*; D003907:Dexamethasone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D004343:Drug Implants / Q000008:administration & dosage*; D005938:Glucocorticoids / Q000008:administration & dosage; D007155:Immunologic Factors / Q000008:administration & dosage; D008262:Macrophage Activation / Q000187:drug effects* / Q000276:immunology*; D008297:Male; D017551:Microdialysis / Q000295:instrumentation / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000276:immunology; D000098902:CD163 Antigen; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018932:Chemokine CCL2; D016207:Cytokines; D003907:Dexamethasone; D004343:Drug Implants; D005938:Glucocorticoids; D007155:Immunologic Factors; D011956:Receptors, Cell Surface; D000098902:CD163 Antigen; C539355:CD68 protein, rat; D000097382:CD68 Molecule; C491766:Ccl2 protein, rat; C004180:dexamethasone 21-phosphate
keywords: CD163; CD68; Dexamethasone; Macrophage activation; Microdialysis