Angiopoietin-2 in experimental colitis

BackgroundThe pathophysiology of inflammatory bowel disease (IBD) includes leukocyte infiltration, blood and lymphatic remodeling, weight loss and protein enteropathy. The roles of angiopoietin-2 (Ang-2) in initiating gut inflammation, leukocyte infiltration and angiogenesis are not well understood.MethodsDisease activity index, histopathological scoring, myeloperoxidase assay, immunohistochemistry and sodium dodecyl sulphate- polyacrylamide gel electrophoretic methods were employed in the present study to addess the roles of Ang-2 in experimental colitis.ResultsSeveral important differences were seen in the development of experimental IBD in Ang-2−/− mice. Although weight change and disease activity differ only slightly in WT and Ang-2−/− + DSS treated mice, leukocyte infiltration, inflammation and blood and lymphatic vessel density is significantly attenuated compared to WT + DSS mice. Gut capillary fragility and water export (stool blood and form) appear significantly earlier in Ang-2−/− + DSS mice vs. WT. Colon lengths were also significantly reduced in Ang-2−/− and gut histopathology was less severe in Ang-2−/− compared to WT + DSS. Lastly, the decrease in serum protein content in WT + DSS was less severe in Ang-2−/− + DSS, thus protein losing enteropathy (PLE) a feature of IBD is relieved by Ang-2−/−.ConclusionThese data demonstrate that in DSS colitis, Ang-2 mediates inflammatory hemangiogenesis, lymphangiogenesis and neutrophil infiltration to reduce some, but not all clinical features of IBD. The implications for Ang-2 manipulation in the development of IBD and other inflammatory diseases and treatments involving Ang-2 are discussed. (Inflamm Bowel Dis 2009)