title: Angiopoietin-2 in experimental colitis.
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 address 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(-/-).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Molecular and Cellular Physiology, Louisiana Health Sciences Centre-Shreveport, Louisiana 71130-3932, USA.
authors.forename: Vijay C
authors.initials: VC
authors.lastname: Ganta
authors.forename: Walter
authors.initials: W
authors.lastname: Cromer
authors.forename: Ginny L
authors.initials: GL
authors.lastname: Mills
authors.forename: James
authors.initials: J
authors.lastname: Traylor
authors.forename: Merilyn
authors.initials: M
authors.lastname: Jennings
authors.forename: Sarah
authors.initials: S
authors.lastname: Daley
authors.forename: Benjamin
authors.initials: B
authors.lastname: Clark
authors.forename: J Michael
authors.initials: JM
authors.lastname: Mathis
authors.forename: Michael
authors.initials: M
authors.lastname: Bernas
authors.forename: Moheb
authors.initials: M
authors.lastname: Boktor
authors.forename: Paul
authors.initials: P
authors.lastname: Jordan
authors.forename: Marlys
authors.initials: M
authors.lastname: Witte
authors.forename: J Steven
authors.initials: JS
authors.lastname: Alexander
mesh_terms: D042702:Angiopoietin-2 / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001798:Blood Proteins / Q000032:analysis; D003092:Colitis / Q000139:chemically induced / Q000276:immunology / Q000473:pathology*; D016264:Dextran Sulfate / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000276:immunology / Q000473:pathology*; D042583:Lymphangiogenesis / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009389:Neovascularization, Pathologic / Q000235:genetics*; D020556:Neutrophil Infiltration / Q000235:genetics*; D015431:Weight Loss / Q000187:drug effects
chemical_list: D042702:Angiopoietin-2; D001798:Blood Proteins; D016264:Dextran Sulfate