Stage-specific expression of mucosal addressin cell adhesion molecule-1 during embryogenesis in rats

Mucosal addressin cell adhesion molecule-1 (MAdCAM-1) is essential for lymp hocyte trafficking to gut-associated lymphoid tissues and is implicated in inflammatory disorders in the gut and pancreatic islets, In this study, we examined the functional role of MAdCAM-1 during rat ontogeny using newly ge nerated specific mAb, As previously observed in mice and humans, MAdCAM-1. was preferentially expressed in high endothelial venules (HEV) in gut-assoc iated lymphoid tissues and venules of lamina propria in adult rats. Lymphoc yte rolling and adhesion on HEV in Peyer's patches (PP) were completely abr ogated with neutralizing anti-MAdCAM-1 mAb, in agreement with the notion th at MAdCAM-1 is the principal HEV ligand for lymphocyte rolling and adhesion in adult PP. In the developing gastrointestinal tract, MAdCAM-1 was widely expressed in the venules of the lamina propria of fetal rats. In addition, MAdCAM-1 was also expressed in follicular dendritic cells in the neonatal PP, Interestingly, MAdCAM-1 expression was found also in nonmucosal tissues during ontogeny, MAdCAM-1 was transiently expressed in blood vascular endo thelial cells in the fetal skin and neonatal thymus, Notably, MAdCAM-1-posi tive blood vessels were localized mainly in the cortico-medullary junction in the neonatal thymus and about 10-20% of thymocytes, most of which were e ither CD4, CD8 double positive or single positive specifically reacted with soluble MAdCAM-1 via integrin alpha(4)beta(7). After birth, MAdCAM-1 expre ssion in thymus blood vessels disappeared and concomitantly, the soluble MA dCAM-1-reactive thymocytes were rapidly down-regulated. Our results suggest that MAdCAM-1 functions as a vascular addressin in not only mucosal, but a lso nonmucosal lymphoid tissues during ontogeny.