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This Article Full Text Full Text (PDF) All Versions of this Article: 294/3/G770    most recent 00453.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ghia, J.-E. Articles by Collins, S. Search for Related Content PubMed PubMed Citation Articles by Ghia, J.-E. Articles by Collins, S.

INFLAMMATION/IMMUNITY/MEDIATORS

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

¹Intestinal Diseases Research Programme, McMaster University, Hamilton, Ontario, Canada; ²Department of Surgical and Gastroenterological Sciences, Padua University, Padua, Italy; ³Department of Medicine, William Osler Health Centre, Brampton, Etobicoke, Ontario, Canada; ⁴Department of Pathology, University of Michigan, Ann Arbor, Michigan; and ⁵Division of Gastroenterology, British Columbia's Children's Hospital, Vancouver, British Columbia, Canada

Submitted 3 October 2007 ; accepted in final form 16 January 2008

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-, IL-1β, 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-, IL-1β, 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-1 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.

macrophages; macrophage colony-stimulating factor; experimental colitis; cytokines; inflammatory bowel disease