1. Lovastatin and phospholipase Cgamma regulate constitutive and protein kinase C dependent integrin mediated interactions of human T-cells with collagen.
- Author
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Bank I, Koltakov A, Nir-Glickman E, Goldstein I, Li J, Roitelman J, and Chess L
- Subjects
- Cell Adhesion drug effects, Cell Adhesion immunology, Cell Adhesion physiology, Collagen Type IV physiology, Flavonoids pharmacology, Flow Cytometry, Herpesvirus 2, Saimiriine immunology, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors pharmacology, Integrin alpha1beta1 antagonists & inhibitors, Integrin alpha1beta1 immunology, Interferon-gamma antagonists & inhibitors, Interferon-gamma immunology, Interferon-gamma metabolism, Lovastatin immunology, MAP Kinase Kinase 1, Mevalonic Acid pharmacology, Mitogen-Activated Protein Kinase Kinases antagonists & inhibitors, Phospholipase C gamma, Pravastatin immunology, Pravastatin pharmacology, Protein Kinase C antagonists & inhibitors, Protein Serine-Threonine Kinases antagonists & inhibitors, T-Lymphocytes metabolism, T-Lymphocytes physiology, Tetradecanoylphorbol Acetate pharmacology, Type C Phospholipases immunology, Type C Phospholipases pharmacology, Collagen Type IV immunology, Integrin alpha1beta1 physiology, Lovastatin pharmacology, Protein Kinase C metabolism, T-Lymphocytes immunology, Type C Phospholipases antagonists & inhibitors
- Abstract
We previously reported that human interleukin (IL)-2 dependent T cell lines derived from very late antigen (VLA)-1(+) CD45RO(+) peripheral blood (PB) T-cells adhere constitutively to collagen type IV, whereas lines from VLA-1(-) PB lymphocytes (L) adhere weakly. Here we report that the latter are induced to adhere by phorbol 12-myristate 13-acetate (PMA). Both PMA dependent and constitutive adhesion, including that of a Herpes Virus Saimiri (HVS) infected CD4(+)VLA-1(+) clone (HVST) were inhibited by anti-VLA-1 monoclonal antibodies (mAb), by inhibitors of phospholipase C (PLC)gamma and by lovastatin but not by a MEK1 inhibitor, whereas only PMA induced adhesion was blocked by inhibition of protein-kinase (PK) C. Furthermore, lovastatin enhanced PLCgamma and anti VLA-1 mAb blockade, and its effect was not reversed by mevalonic acid (MVA). Lovastatin also inhibited interferon (IFN)gamma secretion by T cells triggered with anti-CD3 and in cells detaching from collagen IV. These results suggest new ways for functional modulation of activated T-cells interacting with collagen.
- Published
- 2003
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