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

Ilan Bank, Alexander Koltakov, Eva Nir-Glickman, Itamar Goldstein, Jian Feng Li, Joseph Roitelman, Leonard Chess

Research output: Contribution to journalArticlepeer-review

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)γ 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 PLCγ and anti VLA-1 mAb blockade, and its effect was not reversed by mevalonic acid (MVA). Lovastatin also inhibited interferon (IFN)γ 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.

Original languageEnglish
Pages (from-to)35-45
Number of pages11
JournalCellular Immunology
Volume223
Issue number1
DOIs
StatePublished - May 2003

Keywords

  • CD45RO
  • Collagen
  • Integrin(s)
  • Interferon γ
  • T cells
  • VLA-1
  • α1β1 Integrin

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