title: The spontaneously adhesive leukocyte function-associated antigen-1 (LFA-1) integrin in effector T cells mediates rapid actin- and calmodulin-dependent adhesion strengthening to ligand under shear flow.
abstract: Integrins in effector T cells are highly expressed and important for trafficking of these cells and for their effector functions. However, how integrins are regulated in effector T cells remains poorly characterized. Here, we have investigated effector T cell leukocyte function-associated antigen-1 (LFA-1) regulation in primary murine effector T cells. These cells have high LFA-1 integrin expression and display high spontaneous binding to intercellular adhesion molecule-1 (ICAM-1) ligand under static conditions. In addition, these cells are able to migrate spontaneously on ICAM-1. Atomic force microscopy measurements showed that the force required for unbinding of integrin-ligand interactions increases over time (0.5-20-s contact time). The maximum unbinding force for this interaction was ∼140 piconewtons at 0.5-s contact time, increasing to 580 piconewtons at 20-s contact time. Also, the total work required to disrupt the interaction increased over the 20-s contact time, indicating LFA-1-mediated adhesion strengthening in primary effector T cells over a very quick time frame. Effector T cells adhered spontaneously to ICAM-1 under conditions of shear flow, in the absence of chemokine stimulation, and this binding was independent of protein kinase B/Akt and protein kinase C kinase activity, but dependent on calcium/calmodulin signaling and an intact actin cytoskeleton. These results indicate that effector T cell integrins are highly expressed and spontaneously adhesive in the absence of inside-out integrin signaling but that LFA-1-mediated firm adhesion under conditions of shear flow requires downstream integrin signaling, which is dependent on calcium/calmodulin and the actin cytoskeleton.
authors.affiliation: Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, United Kingdom.
authors.forename: Hwee San
authors.initials: HS
authors.lastname: Lek
authors.forename: Vicky L
authors.initials: VL
authors.lastname: Morrison
authors.forename: Michael
authors.initials: M
authors.lastname: Conneely
authors.forename: Paul A
authors.initials: PA
authors.lastname: Campbell
authors.forename: David
authors.initials: D
authors.lastname: McGloin
authors.forename: Stefanie
authors.initials: S
authors.lastname: Kliche
authors.forename: Colin
authors.initials: C
authors.lastname: Watts
authors.forename: Alan
authors.initials: A
authors.lastname: Prescott
authors.forename: Susanna C
authors.initials: SC
authors.lastname: Fagerholm
mesh_terms: D000199:Actins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D002147:Calmodulin / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D018625:Microscopy, Atomic Force; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D033081:Shear Strength; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D000199:Actins; D002147:Calmodulin; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1; D051057:Proto-Oncogene Proteins c-akt
keywords: Adhesion; Immunology; Integrin; Migration; T Cell Biology