title: Role of M-CSF-dependent macrophages in colitis is driven by the nature of the inflammatory stimulus.
abstract: Although macrophages are considered a critical factor in determining the severity of acute inflammatory responses in the gut, recent evidence has indicated that macrophages may also play a counterinflammatory role. In this study, we examined the role of a macrophage subset in two models of colitis. Macrophage colony-stimulating factor (M-CSF)-deficient osteopetrotic mice (op/op) and M-CSF-expressing heterozygote (+/?) mice were studied following the induction of colitis by either dinitrobenzene sulfonic acid (DNBS) or dextran sulfate sodium (DSS). DNBS induced a severe colitis in M-CSF-deficient op/op mice compared with +/? mice. This was associated with increased mortality and more severe macroscopic and microscopic injury. Colonic tissue myeloperoxidase (MPO) activity as well as concentrations of TNF-alpha, IL-1beta, and IL-6 were higher and IL-10 lower in op/op mice with DNBS colitis. The severity of inflammation and mortality was attenuated in op/op mice that had received human recombinant M-CSF prior to the induction of colitis. In contrast, op/op mice appeared less vulnerable to colitis induced by DSS. Macroscopic damage, microscopic injury, MPO activity, and tissue concentrations of TNF-alpha, IL-1beta, and IL-6 were all lower in op/op mice compared with +/? mice with DSS colitis, and no changes were seen in IL-10. Macrophage inflammatory protein-1alpha concentrations were increased in op/op but not +/? mice following colitis induced by DNBS but not DSS. These results indicate that M-CSF-dependent macrophages may play either a pro- or counterinflammatory role in acute experimental colitis, depending on the stimulus used to induce colitis.
authors.affiliation: Intestinal Diseases Research Programme, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Jean-Eric
authors.initials: JE
authors.lastname: Ghia
authors.forename: Francesca
authors.initials: F
authors.lastname: Galeazzi
authors.forename: David C
authors.initials: DC
authors.lastname: Ford
authors.forename: Cory M
authors.initials: CM
authors.lastname: Hogaboam
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Vallance
authors.forename: Stephen
authors.initials: S
authors.lastname: Collins
mesh_terms: D000818:Animals; D001557:Benzenesulfonates; D003092:Colitis / Q000139:chemically induced / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism; D003627:Data Interpretation, Statistical; D016264:Dextran Sulfate; D004139:Dinitrofluorobenzene / Q000031:analogs & derivatives; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology*; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000502:physiology*; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009195:Peroxidase / Q000378:metabolism; D054389:Receptors, CCR1 / Q000378:metabolism
chemical_list: D001557:Benzenesulfonates; C515301:Ccr1 protein, mouse; D016207:Cytokines; D054389:Receptors, CCR1; C007488:dinitrobenzenesulfonic acid; C045305:2,4-dinitrofluorobenzene sulfonic acid; D016173:Macrophage Colony-Stimulating Factor; D016264:Dextran Sulfate; D004139:Dinitrofluorobenzene; D009195:Peroxidase