Role of M-CSF-dependent macrophages in colitis is driven by the nature of the inflammatory stimulus

Am J Physiol Gastrointest Liver Physiol. 2008 Mar;294(3):G770-7. doi: 10.1152/ajpgi.00453.2007. Epub 2008 Jan 17.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzenesulfonates
  • Colitis / chemically induced
  • Colitis / pathology*
  • Cytokines / metabolism
  • Data Interpretation, Statistical
  • Dextran Sulfate
  • Dinitrofluorobenzene / analogs & derivatives
  • Immunohistochemistry
  • Inflammation / pathology*
  • Macrophage Colony-Stimulating Factor / genetics
  • Macrophage Colony-Stimulating Factor / physiology*
  • Macrophages / physiology*
  • Mice
  • Mice, Knockout
  • Peroxidase / metabolism
  • Receptors, CCR1 / metabolism


  • Benzenesulfonates
  • Ccr1 protein, mouse
  • Cytokines
  • Receptors, CCR1
  • dinitrobenzenesulfonic acid
  • 2,4-dinitrofluorobenzene sulfonic acid
  • Macrophage Colony-Stimulating Factor
  • Dextran Sulfate
  • Dinitrofluorobenzene
  • Peroxidase