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

Anke J Roelofs; Marjo Jauhiainen; Hannu Mönkkönen; Michael J Rogers; Jukka Mönkkönen; Keith Thompson

doi:10.1111/j.1365-2141.2008.07435.x

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

Anke J Roelofs, Marjo Jauhiainen, Hannu Mönkkönen, Michael J Rogers, Jukka Mönkkönen, Keith Thompson^*

^*Corresponding author for this work

Institute of Genetics and Cancer

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	245-50
Number of pages	6
Journal	British journal of haematology
Volume	144
Issue number	2
Early online date	17 Dec 2008
DOIs	https://doi.org/10.1111/j.1365-2141.2008.07435.x
Publication status	Published - Jan 2009

Keywords / Materials (for Non-textual outputs)

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

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Br J Haematol - 2008 - Roelofs - Peripheral blood monocytes are responsible for T cell activation induced by zoledronic
Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.
Final published version, 213 KBLicence: Creative Commons: Attribution (CC-BY)

Cite this

@article{1afb7f770cb745ed922ea23f791bbbdc,

title = "Peripheral blood monocytes are responsible for gammadelta T cell activation induced by zoledronic acid through accumulation of IPP/DMAPP",

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.",

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

author = "Roelofs, \{Anke J\} and Marjo Jauhiainen and Hannu M{\"o}nkk{\"o}nen and Rogers, \{Michael J\} and Jukka M{\"o}nkk{\"o}nen and Keith Thompson",

year = "2009",

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doi = "10.1111/j.1365-2141.2008.07435.x",

language = "English",

volume = "144",

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AU - Roelofs, Anke J

AU - Jauhiainen, Marjo

AU - Mönkkönen, Hannu

AU - Rogers, Michael J

AU - Mönkkönen, Jukka

AU - Thompson, Keith

PY - 2009/1

Y1 - 2009/1

N2 - 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.

AB - 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.

KW - Cell Communication

KW - Cells, Cultured

KW - Diphosphonates/pharmacology

KW - Hemiterpenes/metabolism

KW - Humans

KW - Imidazoles/pharmacology

KW - Lymphocyte Activation

KW - Monocytes/drug effects

KW - Organophosphorus Compounds/metabolism

KW - Receptors, Antigen, T-Cell, gamma-delta/immunology

KW - T-Lymphocytes/drug effects

KW - Zoledronic Acid

U2 - 10.1111/j.1365-2141.2008.07435.x

DO - 10.1111/j.1365-2141.2008.07435.x

M3 - Article

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SN - 0007-1048

VL - 144

SP - 245

EP - 250

JO - British journal of haematology

JF - British journal of haematology

IS - 2

ER -

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

Abstract

Keywords / Materials (for Non-textual outputs)

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