Angiopoietin-2 in experimental colitis.
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.
Ganta
Vijay C
VC
Department of Molecular and Cellular Physiology, Louisiana Health Sciences Centre-Shreveport, Louisiana 71130-3932, USA.
Cromer
Walter
W
Mills
Ginny L
GL
Traylor
James
J
Jennings
Merilyn
M
Daley
Sarah
S
Clark
Benjamin
B
Mathis
J Michael
JM
Bernas
Michael
M
Boktor
Moheb
M
Jordan
Paul
P
Witte
Marlys
M
Alexander
J Steven
JS
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
D042702:Angiopoietin-2; D001798:Blood Proteins; D016264:Dextran Sulfate