VEGF-A stimulation of leukocyte adhesion to colonic microvascular endothelium: implications for inflammatory bowel disease.

Abstract

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder characterized by increased leukocyte recruitment and subsequent tissue damage. An increase in the density of the microvasculature of the colon during IBD has been suggested, leading to the concept that angiogenesis may play a pathological role in IBD. Increased tissue and serum levels of the angiogenic cytokine VEGF-A have been reported in cases of active IBD. In this study, we examined the hypothesis that VEGF-A exerts a proinflammatory effect on colon microvascular endothelium that contributes to colonic inflammation. Leukocyte adhesion to VEGF-A-stimulated colon microvascular endothelial cells was examined using a parallel-plate hydrodynamic flow chamber. ICAM-1 adhesion molecule expression on colonic microvascular endothelium also was determined in response to VEGF-A stimulation, along with characterization of leukocyte adhesion molecule expression. High-dose VEGF-A (50 ng/ml) stimulation increased neutrophil and T cell adhesion to and decreased rolling velocities on activated endothelium, whereas low-dose VEGF-A (10 ng/ml) was without effect. Colonic endothelium constitutively expressed ICAM-1, which was significantly increased by treatment with 50 ng/ml VEGF-A or 10 ng/ml TNF-alpha but not 10 ng/ml VEGF-A. T cells expressed CD18 and CD11a with no expression of CD11b, whereas neutrophils expressed CD18, CD11a, and CD11b. Finally, VEGF-A-dependent leukocyte adhesion was found to occur in a CD18-dependent manner. These results demonstrate that VEGF-A levels found in IBD exert a proinflammatory effect similar to other inflammatory agents and suggest that this cytokine may serve as an intermediary between angiogenic stimulation and cell-mediated immune responses.

• Authors: Stephen Goebel, Meng Huang, William C Davis, Merilyn Jennings, Teruna J Siahaan, J Steven Alexander, Christopher G Kevil
• Journal: American journal of physiology. Gastrointestinal and liver physiology (Am J Physiol Gastrointest Liver Physiol) Vol. 290 Issue 4 Pg. G648-54 (Apr 2006) ISSN: 0193-1857 [Print] United States
• PMID: 16293653 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Angiogenic Proteins
• Vascular Endothelial Growth Factor A
• vascular endothelial growth factor A, mouse

Topics

• Angiogenic Proteins (metabolism)
• Animals
• Cell Adhesion (drug effects, physiology)
• Cells, Cultured
• Colon (blood supply, drug effects, physiology)
• Dose-Response Relationship, Drug
• Endothelium, Vascular (drug effects, physiology)
• Inflammatory Bowel Diseases (physiopathology)
• Leukocytes (physiology)
• Male
• Mice
• Mice, Inbred C57BL
• Microcirculation (drug effects, physiology)
• Vascular Endothelial Growth Factor A (administration & dosage)