Macrophage function in dogs with histiocytic colitis

Histiocytic ulcerative colitis (HUC) is a progressive inflammatory bowel disease (IBD) that occurs predominantly in boxer dogs. The lesions are characterized by mixed inflammatory cell infiltration dominated by PAS-positive macrophages and suggesting a defective immune regulation. Colonic biopsies were obtained from 10 boxer dogs: five with HUC and five unaffected dogs. Serial sections were analyzed for macrophage NFkB expression and apoptotic index. Blood monocytes isolated from peripheral blood by the Bøyum method were cultured overnight in medium containing PMA, LPS or MD.The ability of non- and PMA-stimulated macrophages to reduce nitroblue tetrazolium (NBT) was estimated. LPS- or MD-stimulated macrophages were analyzed by RT-PCR for amplification of genes encoding the cytokines TNF-a , IFN-g, TGF-b, IL-1b, IL-4 and IL-12. Elevated NFkB activity was observed in intestinal epithelial cells and macrophages in mucosal tissue from dogs with HUC. A high percentage of these macrophages were apoptotic. The capacity of non- and PMA-stimulated monocytes from dogs with HUC to reduce NBT was significantly decreased relative to controls. Macrophages from dogs with HUC exhibited a different pattern of cytokine gene expression in response to LPS and MDP stimulation, with low levels of IFN-g and elevated TGF-b/IL-4 mRNA. The high rate of apoptosis in macrophages from dogs with HUC suggests an increased susceptibility to bacterial products. This differential sensitivity was supported by the results of the NBT tests and by the cytokine gene expression profile of cells from dogs withHUC.