Activation-dependent changes in soluble fibronectin binding and expression of beta1 integrin activation epitopes in T cells: relationship to T cell adhesion and migration.
The relationship between activation-dependent changes in beta1 integrin conformation, T cell adhesion to immobilized fibronectin, and T cell migration in vitro was analyzed in this study. Stimulation of Jurkat T cells and peripheral T cells with Mn(2+), the activating beta1 integrin-specific monoclonal antibody (mAb) TS2 /16, CD2, or CD28 stimulation led to increased adhesion, soluble fibronectin (FN) binding and expression of the activation epitope defined by the beta1 integrin mAb HUTS-21. Phorbol 12-myristate 13-acetate treatment increased adhesion, but not soluble FN binding or HUTS-21 epitope expression. In peripheral T cells, CD3 or CD7 stimulation also led to increased adhesion, soluble FN binding and HUTS-21 epitope expression. Soluble FN blocked peripheral T cell adhesion induced by Mn(2+) or TS2/16, but had no effect on adhesion induced by the other integrin-activating signals. In contrast, migration induced by TS2/16, CD2, CD3, CD7 or CD28 stimulation was blocked by excess soluble FN. Phosphoinositide 3-OH kinase (PI 3-K) inhibitors blocked receptor-mediated increases in cell adhesion, but not soluble FN binding or HUTS-21 expression. Migration was similarly unaffected by PI 3-K inhibitors, with the exception of CD7- and CD28-induced migration, which was specifically blocked by LY294,002. These results suggest that activation-dependent changes in beta1 integrin conformation are PI 3-K-independent and are involved in T cell migration but not adhesion.
Woods
M L
ML
Department of Laboratory Medicine, Pathology Center for Immunology, Cancer Center, University of Minnesota Medical School, Minneapolis, USA.
Cabañas
C
C
Shimizu
Y
Y
D018801:CD2 Antigens / Q000502:physiology; D002448:Cell Adhesion; D002465:Cell Movement; D018984:Epitopes, T-Lymphocyte; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D018960:Hyaluronan Receptors / Q000502:physiology; D019012:Integrin beta1 / Q000502:physiology*; D019169:Jurkat Cells; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology*
D018801:CD2 Antigens; D018984:Epitopes, T-Lymphocyte; D005353:Fibronectins; D018960:Hyaluronan Receptors; D019012:Integrin beta1; D019869:Phosphatidylinositol 3-Kinases