title: Lymph node chemokines promote sustained T lymphocyte motility without triggering stable integrin adhesiveness in the absence of shear forces.
abstract: Lymphocyte motility in lymph nodes is regulated by chemokines, but the contribution of integrins to this motility remains obscure. Here we examined lymphocyte migration over CCR7-binding chemokines that 'decorate' lymph node stroma. In a shear-free environment, surface-bound lymph node chemokines but not their soluble counterparts promoted robust and sustained T lymphocyte motility. The chemokine CCL21 induced compartmentalized clustering of the integrins LFA-1 and VLA-4 in motile lymphocytes, but both integrins remained nonadhesive to ligands on lymphocytes, dendritic cells and stroma. The application of shear stress to lymphocytes interacting with CCL21 and integrin ligands promoted robust integrin-mediated adhesion. Thus, lymph node chemokines that promote motility and strongly activate lymphocyte integrins under shear forces fail to stimulate stable integrin adhesiveness in extravascular shear-free environments.
authors.affiliation: Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Eilon
authors.initials: E
authors.lastname: Woolf
authors.forename: Irina
authors.initials: I
authors.lastname: Grigorova
authors.forename: Adi
authors.initials: A
authors.lastname: Sagiv
authors.forename: Valentin
authors.initials: V
authors.lastname: Grabovsky
authors.forename: Sara W
authors.initials: SW
authors.lastname: Feigelson
authors.forename: Ziv
authors.initials: Z
authors.lastname: Shulman
authors.forename: Tanja
authors.initials: T
authors.lastname: Hartmann
authors.forename: Michael
authors.initials: M
authors.lastname: Sixt
authors.forename: Jason G
authors.initials: JG
authors.lastname: Cyster
authors.forename: Ronen
authors.initials: R
authors.lastname: Alon
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement; D054421:Chemokine CCL21 / Q000502:physiology*; D006801:Humans; D016023:Integrins / Q000502:physiology*; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D008198:Lymph Nodes / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008870:Microtubules / Q000502:physiology; D033081:Shear Strength; D013601:T-Lymphocytes / Q000502:physiology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000502:physiology
chemical_list: D054421:Chemokine CCL21; D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1