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.
MeSH terms
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Cell Adhesion / drug effects
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Cell Adhesion / immunology
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Cell Adhesion / physiology
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Collagen Type IV / immunology*
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Collagen Type IV / physiology
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Flavonoids / pharmacology
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Flow Cytometry
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Herpesvirus 2, Saimiriine / immunology
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Humans
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Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
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Integrin alpha1beta1 / antagonists & inhibitors
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Integrin alpha1beta1 / immunology
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Integrin alpha1beta1 / physiology*
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Interferon-gamma / antagonists & inhibitors
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Interferon-gamma / immunology
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Interferon-gamma / metabolism
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Lovastatin / immunology
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Lovastatin / pharmacology*
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MAP Kinase Kinase 1
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Mevalonic Acid / pharmacology
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Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors
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Phospholipase C gamma
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Pravastatin / immunology
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Pravastatin / pharmacology
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Protein Kinase C / antagonists & inhibitors
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Protein Kinase C / metabolism*
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Protein Serine-Threonine Kinases / antagonists & inhibitors
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T-Lymphocytes / immunology*
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T-Lymphocytes / metabolism
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T-Lymphocytes / physiology
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Tetradecanoylphorbol Acetate / pharmacology
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Type C Phospholipases / antagonists & inhibitors*
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Type C Phospholipases / immunology
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Type C Phospholipases / pharmacology
Substances
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Collagen Type IV
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Flavonoids
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Hydroxymethylglutaryl-CoA Reductase Inhibitors
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Integrin alpha1beta1
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Interferon-gamma
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Lovastatin
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Protein Serine-Threonine Kinases
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Protein Kinase C
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MAP Kinase Kinase 1
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MAP2K1 protein, human
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Mitogen-Activated Protein Kinase Kinases
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Type C Phospholipases
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Phospholipase C gamma
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Pravastatin
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Tetradecanoylphorbol Acetate
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Mevalonic Acid
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2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one