Brain endothelial adhesion molecule expression in experimental colitis

Objectives: 1) To determine if endothelial expression of adhesion molecules involved in leukocyte recruitment is increased in the brain and other orga ns in four different models of experimental colitis, and 2) to investigate whether leukocyte infiltration occurs in the brain of colitic animals. Methods: Endothelial vascular cell adhesion molecule-1 (VCAM-1) and interce llular adhesion molecule-1 (ICAM-1) expression was quantified using the dua l radiolabeled antibody technique in rats with trinitrobenzenesulfonic acid (TNBS)-induced colitis, in mice with dextran sulfate sodium (DSS)-induced colitis, in SGID mice reconstituted with CD43RB(high) T-cells, and in IL-10 (-/-) mice. Leukocyte infiltration in the brain of TNBS-induced colitic rat s was assessed by myeloperoxidase activity and immunohistochemical staining with anti-CD43 monoclonal antibody. Results: Marked upregulation of brain endothelial VCAM-1 (2- to 5.5-fold) w as consistently found in colitic animals in the four models studied. Brain VCAM-1 strongly correlated with colon VCAM-1 and colon weight. By contrast, upregulation of brain ICAM-1 in colitic animals was only observed in the C D45RB(high) transfer (3-fold) and the TNBS-induced (1.5-fold models). Heart and muscle VCAM-1 and ICAM-1 were not upregulated in colitic animals in th e majority of models studied. There was no leukocyte infiltration into the brain of TNBS-induced colitic rats. Conclusions: Our study demonstrates a marked and specific upregulation of e ndothelial VCAM-1 in the brain of colitic animals. This activation of cereb ral endothelial cells was not assisted with an infiltration of leukocytes i nto brain tissue.