Angiopoietin-2 in experimental colitis

Vijay C. Ganta, Walter Cromer, Ginny L. Mills, James Traylor, Merilyn Jennings, Sarah Daley, Benjamin Clark, J. Michael Mathis, Michael Bernas, Moheb Boktor, Paul Jordan, Marlys Witte, J. Steven Alexander

Research output: Contribution to journalArticlepeer-review

57 Scopus citations

Abstract

Background: The 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. Methods: Disease 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. Results: Several 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-/-. Conclusion: These 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.

Original languageEnglish
Pages (from-to)1029-1039
Number of pages11
JournalInflammatory Bowel Diseases
Volume16
Issue number6
DOIs
StatePublished - 2010

Keywords

  • Crohn's disease
  • MECA-32
  • Neutrophils
  • Ulcerative colitis
  • VEGFR-3

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