E-Selectin Expression in a Murine Model of Chronic Colitis

Abstract

The objective of this study was to quantify E-selectin surface expression in the colon as well as other tissues in a CD4+ T-cell model of chronic colitis in mice using the newly developed dual radiolabel monoclonal antibody technique. Male SCID mice were reconstituted with either 5 × 105 CD4+ CD45RBlow or CD45RBhigh T-cells isolated from normal CB-17 donor mouse spleens and subsequently monitored for clinical signs of colitis. We found that animals injected with CD45RBhigh but not CD45RBlow T-cells nor PBS developed colitis at 6–8 weeks following reconstitution as assessed by loss of body weight, development of loose stools and/or diarrhea, and histopathology. Concurrent with the onset of distal bowel inflammation was enhanced expression of E-selectin compared to SCID mice injected with PBS or reconstituted with CD45RBlow T-cells, both of which did not develop colitis. We also observed significant increases in E-selectin expression in cecum, small intestine, mesentery, and liver of colitic mice. Our data confirm that reconstitution of SCID mice with CD45RBhigh but not CD45RBlow T-cells induces chronic colitis and demonstrate that this chronic colitis is associated with enhanced expression of an endothelial cell-specific adhesion molecule. Furthermore, our studies demonstrate that reconstitution of SCID mice with CD45RBhigh T-cells enhances E-selectin expression in a variety of tissues distant from the site of active inflammation.