Angiopoietin-2 in Experimental Colitis

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

来源：Inflammatory Bowel Diseases, 2010, 16(6): 1029-1039.

DOI：10.1002/ibd.21150

• MECA-32
• VEGFR-3
• neutrophils
• Crohn's disease
• ulcerative 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 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.

• 出版日期2010-6