Peripheral Blood Monocytes Are Responsible for Gammadelta T Cell Activation Induced by Zoledronic Acid Through Accumulation of IPP/DMAPP

Br J Haematol. 2009 Jan;144(2):245-50. doi: 10.1111/j.1365-2141.2008.07435.x. Epub 2008 Nov 7.

Abstract

Nitrogen-containing bisphosphonates indirectly activate Vgamma9Vdelta2 T cells through inhibition of farnesyl pyrophosphate synthase and intracellular accumulation of isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), but the cells responsible for Vgamma9Vdelta2 T cell activation through IPP/DMAPP accumulation are unknown. Treatment of human peripheral blood mononuclear cells (PBMCs) with a pharmacologically relevant concentration of zoledronic acid induced accumulation of IPP/DMAPP selectively in monocytes, which correlated with efficient drug uptake by these cells. Furthermore, zoledronic acid-pulsed monocytes triggered activation of gammadelta T cells in a cell contact-dependent manner. These observations identify monocytes as the cell type directly affected by bisphosphonates responsible for Vgamma9Vdelta2 T cell activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Communication
  • Cells, Cultured
  • Diphosphonates / pharmacology*
  • Hemiterpenes / metabolism*
  • Humans
  • Imidazoles / pharmacology*
  • Lymphocyte Activation
  • Monocytes / drug effects
  • Monocytes / immunology*
  • Organophosphorus Compounds / metabolism*
  • Receptors, Antigen, T-Cell, gamma-delta / immunology
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • Zoledronic Acid

Substances

  • CGP 58318
  • Diphosphonates
  • Hemiterpenes
  • Imidazoles
  • Organophosphorus Compounds
  • Receptors, Antigen, T-Cell, gamma-delta
  • isopentenyl pyrophosphate
  • 3,3-dimethylallyl pyrophosphate
  • Zoledronic Acid