Peripheral blood monocytes are responsible for γδ T cell activation induced by zoledronic acid through accumulation of IPP/DMAPP

Anke J. Roelofs, Marjo Jauhiainen, Hannu Monkkonen, Michael J. Rogers, Jukka Monkkonen, Keith Thompson

Research output: Contribution to journalArticle

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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 languageEnglish
Pages (from-to)245-250
Number of pages6
JournalBritish Journal of Haematology
Volume144
Issue number2
Early online date11 Nov 2008
DOIs
Publication statusPublished - Jan 2009

Keywords

  • bisphosphonates
  • alkylamines
  • monocytes
  • gamma delta T cells
  • isopentenyl diphosphate
  • bisphosphonate
  • aminobisphosphonates
  • proliferation
  • statins

Cite this

Peripheral blood monocytes are responsible for γδ T cell activation induced by zoledronic acid through accumulation of IPP/DMAPP. / Roelofs, Anke J.; Jauhiainen, Marjo; Monkkonen, Hannu; Rogers, Michael J.; Monkkonen, Jukka; Thompson, Keith.

In: British Journal of Haematology, Vol. 144, No. 2, 01.2009, p. 245-250.

Research output: Contribution to journalArticle

Roelofs, Anke J. ; Jauhiainen, Marjo ; Monkkonen, Hannu ; Rogers, Michael J. ; Monkkonen, Jukka ; Thompson, Keith. / Peripheral blood monocytes are responsible for γδ T cell activation induced by zoledronic acid through accumulation of IPP/DMAPP. In: British Journal of Haematology. 2009 ; Vol. 144, No. 2. pp. 245-250.
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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.",
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AB - 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.

KW - bisphosphonates

KW - alkylamines

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