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 J Bernas, Moheb Boktor, Paul Jordan, Marlys H Witte, J. Steven Alexander

Research output: Contribution to journalArticle

51 Citations (Scopus)

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

Fingerprint

Angiopoietin-2
Colitis
Inflammatory Bowel Diseases
Leukocytes
Capillary Fragility
Protein-Losing Enteropathies
Lymphangiogenesis
Inflammation
Lymphatic Vessels
Neutrophil Infiltration
Sodium Dodecyl Sulfate
Peroxidase
Blood Vessels
Blood Proteins
Weight Loss

Keywords

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

ASJC Scopus subject areas

  • Gastroenterology
  • Immunology and Allergy

Cite this

Ganta, V. C., Cromer, W., Mills, G. L., Traylor, J., Jennings, M., Daley, S., ... Alexander, J. S. (2010). Angiopoietin-2 in experimental colitis. Inflammatory Bowel Diseases, 16(6), 1029-1039. https://doi.org/10.1002/ibd.21150

Angiopoietin-2 in experimental colitis. / Ganta, Vijay C.; Cromer, Walter; Mills, Ginny L.; Traylor, James; Jennings, Merilyn; Daley, Sarah; Clark, Benjamin; Mathis, J. Michael; Bernas, Michael J; Boktor, Moheb; Jordan, Paul; Witte, Marlys H; Alexander, J. Steven.

In: Inflammatory Bowel Diseases, Vol. 16, No. 6, 2010, p. 1029-1039.

Research output: Contribution to journalArticle

Ganta, VC, Cromer, W, Mills, GL, Traylor, J, Jennings, M, Daley, S, Clark, B, Mathis, JM, Bernas, MJ, Boktor, M, Jordan, P, Witte, MH & Alexander, JS 2010, 'Angiopoietin-2 in experimental colitis', Inflammatory Bowel Diseases, vol. 16, no. 6, pp. 1029-1039. https://doi.org/10.1002/ibd.21150
Ganta VC, Cromer W, Mills GL, Traylor J, Jennings M, Daley S et al. Angiopoietin-2 in experimental colitis. Inflammatory Bowel Diseases. 2010;16(6):1029-1039. https://doi.org/10.1002/ibd.21150
Ganta, Vijay C. ; Cromer, Walter ; Mills, Ginny L. ; Traylor, James ; Jennings, Merilyn ; Daley, Sarah ; Clark, Benjamin ; Mathis, J. Michael ; Bernas, Michael J ; Boktor, Moheb ; Jordan, Paul ; Witte, Marlys H ; Alexander, J. Steven. / Angiopoietin-2 in experimental colitis. In: Inflammatory Bowel Diseases. 2010 ; Vol. 16, No. 6. pp. 1029-1039.
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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.",
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AB - 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.

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