Abstract
Nitrogen-containing bisphosphonates indirectly activate Vγ9Vδ2 T cells through inhibition of farnesyl pyrophosphate synthase and intracellular accumulation of isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), but the cells responsible for Vγ9Vδ2 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 γδ T cells in a cell contact-dependent manner. These observations identify monocytes as the cell type directly affected by bisphosphonates responsible for Vγ9Vδ2 T cell activation.
Original language | English |
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Pages (from-to) | 245-250 |
Number of pages | 6 |
Journal | British Journal of Haematology |
Volume | 144 |
Issue number | 2 |
Early online date | 11 Nov 2008 |
DOIs | |
Publication status | Published - Jan 2009 |
Keywords
- bisphosphonates
- alkylamines
- monocytes
- gamma delta T cells
- isopentenyl diphosphate
- bisphosphonate
- aminobisphosphonates
- proliferation
- statins