title: The roles of L-selectin, beta 7 integrins, and P-selectin in leukocyte rolling and adhesion in high endothelial venules of Peyer's patches.
abstract: Lymphocyte trafficking into Peyer's patches requires beta 7 integrins and L-selectin. Here, we use intravital microscopy to examine leukocyte rolling and adhesion in Peyer's patch high endothelial venules (HEV) of wild-type, L-selectin-deficient (L-/-), beta 7 integrin-deficient (beta 7-/-), and beta 7/L(-/-) mice. Although the leukocyte rolling flux fraction was reduced by 70%, Peyer's patches in L-/- mice were of normal size and cellularity. In beta 7-/- mice, the rolling flux fraction was normal, but the number of adherent leukocytes in HEV was greatly reduced. The median leukocyte rolling velocity was reduced in L-/- mice and increased in beta 7-/- mice, suggesting that beta 7 integrins and L-selectin mediate rolling in Peyer's patch HEV at different velocities. beta 7/L(-/-) exhibited both a low rolling flux fraction and low adhesion and had severely reduced Peyer's patch size and cellularity. The residual rolling in these mice was completely blocked by a P-selectin mAb. A significant P-selectin component was also detected in the other genotypes. Twenty-six percent of B and T lymphocytes isolated from Peyer's patches of wild-type mice expressed functional ligands for P-selectin, and this fraction was increased to 57% in beta 7/L(-/-) mice. Peyer's patch HEV were found to express P-selectin under the conditions of intravital microscopy, but not in situ. Our data suggest a novel P-selectin dependent mechanism of lymphocyte homing to Peyer's patches. In situ, beta 7 integrins and L-selectin account for all lymphocyte homing to Peyer's patches, but P-selectin-dependent rolling, as induced by minimal trauma, may support trafficking of effector T lymphocytes to Peyer's patches.
authors.affiliation: Department of Biomedical Engineering, University of Virginia School of Medicine, Charlottesville 22908, USA.
authors.forename: E J
authors.initials: EJ
authors.lastname: Kunkel
authors.forename: C L
authors.initials: CL
authors.lastname: Ramos
authors.forename: D A
authors.initials: DA
authors.lastname: Steeber
authors.forename: W
authors.initials: W
authors.lastname: Müller
authors.forename: N
authors.initials: N
authors.lastname: Wagner
authors.forename: T F
authors.initials: TF
authors.lastname: Tedder
authors.forename: K
authors.initials: K
authors.lastname: Ley
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity / Q000276:immunology; D002448:Cell Adhesion / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D004729:Endothelium, Lymphatic / Q000098:blood supply / Q000378:metabolism / Q000502:physiology*; D039641:Integrin beta Chains; D016023:Integrins / Q000235:genetics / Q000502:physiology*; D019041:L-Selectin / Q000235:genetics / Q000502:physiology*; D007958:Leukocyte Count; D007962:Leukocytes / Q000502:physiology*; D008214:Lymphocytes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019007:P-Selectin / Q000096:biosynthesis / Q000502:physiology*; D010581:Peyer's Patches / Q000098:blood supply / Q000166:cytology / Q000502:physiology*; D011485:Protein Binding / Q000276:immunology
chemical_list: D039641:Integrin beta Chains; D016023:Integrins; D019007:P-Selectin; C091368:integrin beta7; D019041:L-Selectin