DISTINCT ROLES OF L-SELECTIN AND INTEGRINS ALPHA-4-BETA-7 AND LFA-1 IN LYMPHOCYTE HOMING TO PEYERS PATCH-HEV IN-SITU - THE MULTISTEP MODEL CONFIRMED AND REFINED

Circulating lymphocytes home to the mucosal lymphoid organs, Peyer's patches (PP), through high endothelial venules (HEV). In situ analyses revealed that transfused lymph node cells (LNCs) interact with PP-HEV in a series of overlapping adhesion events: L-selectin (CD62L) >alpha 4 beta 7 initiates interaction, L-selectin and alpha 4 beta 7 both participate in rolling, and Gal-linked activation triggers arrest that requires both alpha 4 beta 7 and LFA-1. alpha 4 beta 7 dramatically reduces rolling velocity, and appears to be required for engagement of LFA-1. In contrast with resting LNC, preactivated LNC or alpha 4 beta 7(hi) lymphoma cells require only alpha 4 beta 7 for arrest in PP-HEV. The predominant PP-HEV ligand for alpha 4 beta 7 but also apparently for L-selectin is the mucosal addressin MAd-CAM-1. These results validate the concept of multimolecular adhesion/decision cascades in physiologic lymphocyte-endothelial recognition, define a novel role for alpha 4 integrins as a ''bridge'' between selectin and beta 2 integrin-dependent events, and reemphasize the potential for direct adhesion through preactivated alpha 4 integrins alone.