Submitted on October 3, 2007
Accepted on January 16, 2008
Role of M-CSF dependent macrophages in colitis is driven by the nature of the inflammatory stimulus
Jean-Eric Ghia1, Francesca Galeazzi2, David C Ford3, Cory M. Hogaboam4, Bruce A Vallance5, and Stephen M. Collins6*
1 IDRP, McMaster Univeristy, Hamilton, Canada
2 Department of Surgical and Gastroenterological Sciences, Padua University, Padua, Italy
3 Department of Medicine, William Osler Health Centre, Etobicoke, Canada
4 Pathology, University of Michigan, Ann Arbor, Michigan, United States
5 Pediatrics, UBC, Vancouver, Canada
6 IDRP, Mcmaster Universtity, Hamilton, Canada
* To whom correspondence should be addressed. E-mail: scollins{at}mcmaster.ca.
While 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 counter-inflammatory role. In this study, we examined the role of a macrophage subset in two models of colitis. Macrophages-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 to +/? mice. This was associated with increased mortality and more severe macroscopic and microscopic injury. Colonic tissue myeloperoxidase activity (MPO) as well as concentrations of TNF-a, IL-1b 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 hr-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-a, IL-1b and IL-6 were all lower in op/op mice compared to +/? mice with DSS colitis and no changes were seen in IL-10. MIP-1a 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 counter-inflammatory role in acute experimental colitis, depending on the stimulus used to induce colitis.
