E-selectin expression in a murine model of chronic colitis

The objective of this study was to quantify E-selectin surface expression i n the colon as well as other tissues in a CD4+ T-cell model of chronic coli tis in mice using the newly developed dual radiolabel monoclonal antibody t echnique. Male SCID mice were reconstituted with either 5 x 10(5) CD4+ CD45 RB(low) or CD45RB(high) T-cells isolated from normal CB-17 donor mouse sple ens and subsequently monitored for clinical signs of colitis. We found that animals injected with CD45RB(high) but not CD45RB(low) T-cells nor PBS dev eloped colitis at 6-8 weeks following reconstitution as assessed by loss of body weight, development of loose stools and/or diarrhea, and histopatholo gy. Concurrent with the onset of distal bowel inflammation was enhanced exp ression of E-selectin compared to SCID mice injected with PBS or reconstitu ted with CD45RB(low) T-cells, both of which did not develop colitis. We als o observed significant increases in E-selectin expression in cecum, small i ntestine, mesentery, and liver of colitic mice. Our data confirm that recon stitution of SCID mice with CD45RB(high) but not CD45RB(low) T-cells induce s chronic colitis and demonstrate that this chronic colitis is associated w ith enhanced expression of an endothelial cell-specific adhesion molecule. Furthermore, our studies demonstrate that reconstitution of SCID mice with CD45RB(high) T-cells enhances E-selectin expression in a variety of tissues distant from the site of active inflammation. (C) 2000 Academic Press.