Lovastatin and phospholipase Cgamma regulate constitutive and protein kinase C dependent integrin mediated interactions of human T-cells with collagen.
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.
Bank
Ilan
I
Department of Medicine F, Chaim Sheba Medical Center, Tel Aviv University, Tel Hashomer 52621, Israel. ibank@post.tau.ac.il
Koltakov
Alexander
A
Nir-Glickman
Eva
E
Goldstein
Itamar
I
Li
JianFeng
J
Roitelman
Joseph
J
Chess
Leonard
L
D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D024141:Collagen Type IV / Q000276:immunology* / Q000502:physiology; D005419:Flavonoids / Q000494:pharmacology; D005434:Flow Cytometry; D006567:Herpesvirus 2, Saimiriine / Q000276:immunology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D039222:Integrin alpha1beta1 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D008148:Lovastatin / Q000276:immunology / Q000494:pharmacology*; D048369:MAP Kinase Kinase 1; D008798:Mevalonic Acid / Q000494:pharmacology; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D051966:Phospholipase C gamma; D017035:Pravastatin / Q000276:immunology / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000494:pharmacology
D024141:Collagen Type IV; D005419:Flavonoids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D039222:Integrin alpha1beta1; D007371:Interferon-gamma; D008148:Lovastatin; D017346:Protein Serine-Threonine Kinases; D011493:Protein Kinase C; D048369:MAP Kinase Kinase 1; C482125:MAP2K1 protein, human; D020929:Mitogen-Activated Protein Kinase Kinases; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D017035:Pravastatin; D013755:Tetradecanoylphorbol Acetate; D008798:Mevalonic Acid; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one