Cytokines stimulate the release of microvesicles from myeloid cells independently from the P2X7 receptor/acid sphingomyelinase pathway

F Colombo, M Bastoni, A Nigro, P Podini, A Finardi, Giacomo Casella, M Ramesh, C Farina, C Verderio, R Furlan

Research output: Contribution to journalArticle

Abstract

Microvesicles (MVs) are membrane particles of 200-500 nm released by all cell types constitutively. MVs of myeloid origin are found increased in the cerebrospinal fluid (CSF) of patients suffering from neuroinflammatory disorders, although the factors triggering their production have never been defined. Here, we report that both pro- and anti-inflammatory cytokines, specifically interferon-γ and interleukin-4, are equally able to stimulate the production of MVs from microglia cells and monocytes. Additionally, we found this process to be independent from the best characterized molecular pathway so far described for membrane shedding, which is centered on the purinergic receptor P2X7, whose activation by high concentrations of extracellular ATP (exATP) results in membrane blebbing operated by the secreted enzyme acid sphingomyelinase (ASMase). Moreover, a potent inhibitor of ASMase, injected in a mouse model of multiple sclerosis, failed to reduce the number of MVs in their CSF. This suggests that cytokines, rather than exATP, may exert a long-term control of MV production in the context of chronic inflammation, where both pro- and anti-inflammatory factors play coordinated roles. © 2018 Colombo, Bastoni, Nigro, Podini, Finardi, Casella, Ramesh, Farina, Verderio and Furlan.
Original languageEnglish
Article number204
JournalFrontiers in Immunology
Volume9
Issue number3
DOIs
Publication statusPublished - 2018

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Purinergic P2X7 Receptors
Sphingomyelin Phosphodiesterase
Myeloid Cells
Cytokines
Acids
Membranes
Cerebrospinal Fluid
Anti-Inflammatory Agents
Adenosine Triphosphate
Microglia
Blister
Interleukin-4
Interferons
Multiple Sclerosis
Monocytes
Inflammation
Enzymes

Cite this

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title = "Cytokines stimulate the release of microvesicles from myeloid cells independently from the P2X7 receptor/acid sphingomyelinase pathway",
abstract = "Microvesicles (MVs) are membrane particles of 200-500 nm released by all cell types constitutively. MVs of myeloid origin are found increased in the cerebrospinal fluid (CSF) of patients suffering from neuroinflammatory disorders, although the factors triggering their production have never been defined. Here, we report that both pro- and anti-inflammatory cytokines, specifically interferon-γ and interleukin-4, are equally able to stimulate the production of MVs from microglia cells and monocytes. Additionally, we found this process to be independent from the best characterized molecular pathway so far described for membrane shedding, which is centered on the purinergic receptor P2X7, whose activation by high concentrations of extracellular ATP (exATP) results in membrane blebbing operated by the secreted enzyme acid sphingomyelinase (ASMase). Moreover, a potent inhibitor of ASMase, injected in a mouse model of multiple sclerosis, failed to reduce the number of MVs in their CSF. This suggests that cytokines, rather than exATP, may exert a long-term control of MV production in the context of chronic inflammation, where both pro- and anti-inflammatory factors play coordinated roles. {\circledC} 2018 Colombo, Bastoni, Nigro, Podini, Finardi, Casella, Ramesh, Farina, Verderio and Furlan.",
author = "F Colombo and M Bastoni and A Nigro and P Podini and A Finardi and Giacomo Casella and M Ramesh and C Farina and C Verderio and R Furlan",
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TY - JOUR

T1 - Cytokines stimulate the release of microvesicles from myeloid cells independently from the P2X7 receptor/acid sphingomyelinase pathway

AU - Colombo, F

AU - Bastoni, M

AU - Nigro, A

AU - Podini, P

AU - Finardi, A

AU - Casella, Giacomo

AU - Ramesh, M

AU - Farina, C

AU - Verderio, C

AU - Furlan, R

PY - 2018

Y1 - 2018

N2 - Microvesicles (MVs) are membrane particles of 200-500 nm released by all cell types constitutively. MVs of myeloid origin are found increased in the cerebrospinal fluid (CSF) of patients suffering from neuroinflammatory disorders, although the factors triggering their production have never been defined. Here, we report that both pro- and anti-inflammatory cytokines, specifically interferon-γ and interleukin-4, are equally able to stimulate the production of MVs from microglia cells and monocytes. Additionally, we found this process to be independent from the best characterized molecular pathway so far described for membrane shedding, which is centered on the purinergic receptor P2X7, whose activation by high concentrations of extracellular ATP (exATP) results in membrane blebbing operated by the secreted enzyme acid sphingomyelinase (ASMase). Moreover, a potent inhibitor of ASMase, injected in a mouse model of multiple sclerosis, failed to reduce the number of MVs in their CSF. This suggests that cytokines, rather than exATP, may exert a long-term control of MV production in the context of chronic inflammation, where both pro- and anti-inflammatory factors play coordinated roles. © 2018 Colombo, Bastoni, Nigro, Podini, Finardi, Casella, Ramesh, Farina, Verderio and Furlan.

AB - Microvesicles (MVs) are membrane particles of 200-500 nm released by all cell types constitutively. MVs of myeloid origin are found increased in the cerebrospinal fluid (CSF) of patients suffering from neuroinflammatory disorders, although the factors triggering their production have never been defined. Here, we report that both pro- and anti-inflammatory cytokines, specifically interferon-γ and interleukin-4, are equally able to stimulate the production of MVs from microglia cells and monocytes. Additionally, we found this process to be independent from the best characterized molecular pathway so far described for membrane shedding, which is centered on the purinergic receptor P2X7, whose activation by high concentrations of extracellular ATP (exATP) results in membrane blebbing operated by the secreted enzyme acid sphingomyelinase (ASMase). Moreover, a potent inhibitor of ASMase, injected in a mouse model of multiple sclerosis, failed to reduce the number of MVs in their CSF. This suggests that cytokines, rather than exATP, may exert a long-term control of MV production in the context of chronic inflammation, where both pro- and anti-inflammatory factors play coordinated roles. © 2018 Colombo, Bastoni, Nigro, Podini, Finardi, Casella, Ramesh, Farina, Verderio and Furlan.

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DO - 10.3389/fimmu.2018.00204

M3 - Article

VL - 9

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

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M1 - 204

ER -