title: The direction of migration of T-lymphocytes under flow depends upon which adhesion receptors are engaged.
abstract: T-lymphocyte migration is important for homing, cell trafficking, and immune surveillance. T-lymphocytes express lymphocyte function-associated antigen-1 (LFA-1; αLβ2) and very late antigen-4 (VLA-4; α4β1), which bind to their cognate ligands, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). These adhesive interactions provide T-lymphocytes with the ability to withstand hemodynamic shear forces to facilitate adhesion and migration along the blood endothelium. Recently, it has been shown that T-lymphocytes will crawl upstream against the direction of flow on surfaces functionalized with ICAM-1. Here, we have investigated whether the identity of the receptor and the magnitude of its engagement affects the direction of T-lymphocyte migration under flow. We used microcontact printed ICAM-1 and VCAM-1 PDMS surfaces on which density and type of adhesion molecule can be tightly controlled and non-specific adhesion adequately blocked. Using a laminar flow chamber, we demonstrate that T-lymphocytes migrate either upstream or downstream dependent upon ligand type, ligand concentration and shear rate. T-lymphocytes were found to migrate upstream on ICAM-1 but downstream on VCAM-1 surfaces - a behavior unique to T-lymphocytes. By varying concentrations of ICAM-1 and VCAM-1, directed migration under flow was observed to be dependent upon the type and concentration of ligand. As shear rates increase, T-lymphocytes favor upstream migration when any ICAM-1 is present, even in the presence of substantial amounts of VCAM-1. Furthermore, a loss of cytoskeletal polarity was observed upon introduction of fluid flow with reorganization that is dependent upon ligand presentation. These results indicate that T-lymphocytes exhibit two different modes of motility - upstream or downstream - under fluid flow that depends on ligand composition and the shear rate.
authors: Department of Bioengineering, University of Pennsylvania, 210 S. 33rd St, Philadelphia, PA 19104, USA. hammer@seas.upenn.edu.
authors: George A
authors: GA
authors: Dominguez
authors: Nicholas R
authors: NR
authors: Anderson
authors: Daniel A
authors: DA
authors: Hammer
mesh_terms: D016880:Anisotropy; D001783:Blood Flow Velocity / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D033081:Shear Strength / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology* / Q000502:physiology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
chemical_list: D015815:Cell Adhesion Molecules; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1