Peripheral blood monocytes are responsible for gammadelta T cell activation induced by zoledronic acid through accumulation of IPP/DMAPP.
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.
Roelofs
Anke J
AJ
Bone and Musculoskeletal Research Programme, Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK.
Jauhiainen
Marjo
M
Mönkkönen
Hannu
H
Rogers
Michael J
MJ
Mönkkönen
Jukka
J
Thompson
Keith
K
D002450:Cell Communication; D002478:Cells, Cultured; D004164:Diphosphonates / Q000494:pharmacology*; D045782:Hemiterpenes / Q000378:metabolism*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D008213:Lymphocyte Activation; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D009943:Organophosphorus Compounds / Q000378:metabolism*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D000077211:Zoledronic Acid
C538827:CGP 58318; D004164:Diphosphonates; D045782:Hemiterpenes; D007093:Imidazoles; D009943:Organophosphorus Compounds; D016692:Receptors, Antigen, T-Cell, gamma-delta; C004809:isopentenyl pyrophosphate; C043060:3,3-dimethylallyl pyrophosphate; D000077211:Zoledronic Acid