Lovastatin and phospholipase Cgamma regulate constitutive and protein kinase C dependent integrin mediated interactions of human T-cells with collagen

Cell Immunol. 2003 May;223(1):35-45. doi: 10.1016/s0008-8749(03)00147-3.

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

  • Cell Adhesion / drug effects
  • Cell Adhesion / immunology
  • Cell Adhesion / physiology
  • Collagen Type IV / immunology*
  • 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
  • Integrin alpha1beta1 / physiology*
  • Interferon-gamma / antagonists & inhibitors
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Lovastatin / immunology
  • Lovastatin / pharmacology*
  • 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 Kinase C / metabolism*
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / physiology
  • Tetradecanoylphorbol Acetate / pharmacology
  • Type C Phospholipases / antagonists & inhibitors*
  • Type C Phospholipases / immunology
  • Type C Phospholipases / pharmacology

Substances

  • Collagen Type IV
  • Flavonoids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Integrin alpha1beta1
  • Interferon-gamma
  • Lovastatin
  • Protein-Serine-Threonine Kinases
  • Protein Kinase C
  • MAP Kinase Kinase 1
  • MAP2K1 protein, human
  • Mitogen-Activated Protein Kinase Kinases
  • Type C Phospholipases
  • Phospholipase C gamma
  • Pravastatin
  • Tetradecanoylphorbol Acetate
  • Mevalonic Acid
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one