title: Murine antigen-induced inflammation--a model for studying induction, resolution and the adaptive phase of inflammation.
abstract: Murine zymosan-induced peritonitis is the model most frequently used to study resolution of inflammation. However, the antigen-induced peritonitis model may be better suited for studying resolution of inflammation and the adaptive phase that follows. The objective of this study was to provide an evaluation of the kinetics of cells and mediators during induction, resolution and the adaptive immune phases of a murine antigen-induced inflammation. Female C57BL/6 mice were immunized twice subcutaneously with mBSA and three weeks after the initial immunization they were injected intraperitoneally (i.p.) with mBSA, which induced peritonitis. Peritoneal cells were counted and expression of surface molecules and chemokine receptors analyzed with flow cytometry. Chemokine and cytokine concentrations in peritoneal fluid were determined by ELISA. Two neutrophil populations, differing in size and granularity and slightly in expression of surface molecules, were observed in the peritoneal cavity after induction of inflammation. Macrophages disappeared from the peritoneal cavity following i.p. administration of mBSA but appeared again as they differentiated from recruited monocytes and peaked in numbers at 48 h. At that time point, two distinct populations of macrophages were present in the peritoneal cavity; one with high expression of F4/80, also expressing the atypical chemokine receptor D6 as well as CCR7; the other expressing low levels of F4/80 and also expressing CD11c and CD138. Eosinophils appeared in the peritoneum 3h following i.p. administration of mBSA and peaked at 48 h. At that time point they had upregulated their expression of CCR3 but decreased their expression of CD11b. Peritoneal levels of CCL11 peaked at 6h and may have led to recruitment of the eosinophils. NK cells and T cells peaked at 48 h, whereas B cells peaked at 5 days, with the majority being B1 cells. Peritoneal concentrations of pro-inflammatory cytokines (IL-β and IL-6) and chemokines (CCL2 and CCL3) peaked at 3h, whereas IL-1ra peaked at 6h, sTNF-R at 24h and sIL-6R and TGF-β at 48 h. The results show kinetic alterations in cell populations and mediators in a murine model that may be an excellent model to study initiation and resolution of inflammation and the following adaptive phase.
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Medicine, Biomedical Center, University of Iceland, Reykjavik, Iceland; Department of Immunology, Faculty of Medicine, Biomedical Center, University of Iceland, Reykjavik, Iceland.
authors.forename: Valgerdur
authors.initials: V
authors.lastname: Tomasdottir
authors.affiliation: Center for Rheumatology Research, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland.
authors.forename: Arnor
authors.initials: A
authors.lastname: Vikingsson
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Medicine, Biomedical Center, University of Iceland, Reykjavik, Iceland.
authors.forename: Ingibjorg
authors.initials: I
authors.lastname: Hardardottir
authors.affiliation: Department of Immunology, Faculty of Medicine, Biomedical Center, University of Iceland, Reykjavik, Iceland; Department of Immunology, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland; Center for Rheumatology Research, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland. Electronic address: jonaf@landspitali.is.
authors.forename: Jona
authors.initials: J
authors.lastname: Freysdottir
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D039521:CD11c Antigen / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis* / Q000378:metabolism; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology / Q000473:pathology; D005260:Female; D015870:Gene Expression; D007274:Injections, Intraperitoneal; D007694:Killer Cells, Natural / Q000276:immunology / Q000473:pathology; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology* / Q000473:pathology; D010529:Peritoneal Cavity / Q000473:pathology; D010538:Peritonitis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D054397:Receptors, CCR3 / Q000235:genetics / Q000276:immunology; D012710:Serum Albumin, Bovine; D053668:Syndecan-1 / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
chemical_list: D000943:Antigens, Differentiation; D039521:CD11c Antigen; C515351:Ccr3 protein, mouse; D016207:Cytokines; D054397:Receptors, CCR3; C508242:Sdc1 protein, mouse; D053668:Syndecan-1; C036763:monocyte-macrophage differentiation antigen; D012710:Serum Albumin, Bovine
keywords: Antigen-induced inflammation; Induction of inflammation; Murine model; Resolution of inflammation