ALPHA-4-BETA-7-INTEGRIN MEDIATES LYMPHOCYTE BINDING TO THE MUCOSAL VASCULAR ADDRESSIN MADCAM-1

The mucosal vascular addressin, MAdCAM-1, is an immunoglobulin superfamily adhesion molecule for lymphocytes that is expressed by mucosal venules and helps direct lymphocyte traffic into Peyer's patches (PP) and the intestinal lamina propria. We demonstrate that the lymphocyte integrin alpha4beta7, also implicated in homing to PP, is a receptor for MAdCAM-1. Certain antibodies to alpha4 and beta7 integrin chains but not to the beta2 integrin LFA-1 inhibit lymphocyte binding to purified MAdCAM-1 and to MAdCAM-1 transfectants. Lymph node lymphocytes, alpha4beta7+ TK1 lymphoma cells, and a beta7-transfected variant of an alpha4 + B cell line, 38C13, bind constitutively to MAdCAM-1. Binding is enhanced by Mn++-induced integrin activation. The related integrin alpha4beta1 supports efficient binding to VCAM-1 but not to MAdCAM-1, even after integrin activation, indicating that MAdCAM-1 is a preferential ligand for alpha4beta7. alpha4beta7 can also bind VCAM-1, but this requires greater integrin activation than binding to MAdCAM-1. The findings imply a selective role for the interaction of alpha4beta7 and MAdCAM-1 lymphocyte in homing to mucosal sites.