α4β7 integrin-mediated lymphocyte adhesion to VCAM-1 under physiologic shear requires L-selectin function (P5116)

Abstract Lymphocyte migration is facilitated by a cascade of adhesion molecule interactions. Specifically, lymphocyte rolling is mediated by selectins, while slow rolling and adhesion are attributed to integrin and Ig family members. α4β7 integrin interactions with its primary ligand, MAdCAM-1, synergize with L-selectin function to regulate the recirculation of naïve lymphocytes to the gut. However, subsets of regulatory T cells also express high levels of L-selectin and α4β7 integrin, and may instead bind to VCAM-1, a secondary ligand for α4β7 integrin. Therefore, potential synergism between L-selectin function and α4β7 integrin/VCAM-1 interactions were examined. To determine the ability of α4β7 integrin to interact with VCAM-1 under conditions of shear, transfected TK-1 T cell interactions with EA.hy926 endothelial cell lines were assessed using an in vitro flow chamber assay. While TK-1 cells, expressing α4β7 but not α4β1 integrin, showed little interaction with VCAM-1-transfected endothelial cells, the presence of L-selectin function enabled α4β7 integrin/VCAM-1 interactions to support slow rolling and adhesion. Importantly, α4β7 integrin interactions with VCAM-1 supported slow rolling and adhesion of murine regulatory T cells under shear stress in the presence of L-selectin function. Thus, functional synergy between L-selectin and α4β7 integrin/VCAM-1 interactions may promote regulatory T cell recruitment to sites of inflammation.