title: Distinct roles of L-selectin and integrins alpha 4 beta 7 and LFA-1 in lymphocyte homing to Peyer's patch-HEV in situ: the multistep model confirmed and refined.
abstract: 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 G alpha i-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 7hi 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.
authors.affiliation: Department of Pathology, Stanford University School of Medicine, California 94305, USA.
authors.forename: R F
authors.initials: RF
authors.lastname: Bargatze
authors.forename: M A
authors.initials: MA
authors.lastname: Jutila
authors.forename: E C
authors.initials: EC
authors.lastname: Butcher
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000276:immunology*; D002465:Cell Movement; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology; D039441:Integrin alpha4; D019041:L-Selectin; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D018715:Microscopy, Video; D010581:Peyer's Patches / Q000098:blood supply / Q000166:cytology / Q000276:immunology*; D016201:Receptors, Lymphocyte Homing / Q000276:immunology; D014680:Veins / Q000166:cytology
chemical_list: D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D016169:Lymphocyte Function-Associated Antigen-1; D016201:Receptors, Lymphocyte Homing; D019041:L-Selectin; D039441:Integrin alpha4