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

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.