Myeloid microvesicles are a marker and therapeutic target for neuroinflammation

Claudia Verderio, Luca Muzio, Elena Turola, Alessandra Bergami, Luisa Novellino, Francesca Ruffini, Loredana Riganti, Irene Corradini, Maura Francolini, Livia Garzetti, Chiara Maiorino, Federica Servida, Alessandro Vercelli, Mara Rocca, Dacia Dalla Libera, Vittorio Martinelli, Giancarlo Comi, Gianvito Martino, Michela Matteoli, Roberto Furlan

Research output: Contribution to journalArticle

Abstract

Objective: Microvesicles (MVs) have been indicated as important mediators of intercellular communication and are emerging as new biomarkers of tissue damage. Our previous data indicate that reactive microglia/macrophages release MVs in vitro. The aim of the study was to evaluate whether MVs are released by microglia/macrophages in vivo and whether their number varies in brain inflammatory conditions, such as multiple sclerosis (MS). Methods: Electron and fluorescence microscopy and flow cytometry were used to detect myeloid MVs in the cerebrospinal fluid (CSF) of healthy controls, MS patients, and rodents affected by experimental autoimmune encephalomyelitis (EAE), the animal model of MS. Results: Myeloid MVs were detected in CSF of healthy controls. In relapsing and remitting EAE mice, the concentration of myeloid MVs in the CSF was significantly increased and closely associated with disease course. Analysis of MVs in the CSF of 28 relapsing patients and 28 patients with clinical isolated syndrome from 2 independent cohorts revealed higher levels of myeloid MVs than in 13 age-matched controls, indicating a clinical value of MVs as a companion tool to capture disease activity. Myeloid MVs were found to spread inflammatory signals both in vitro and in vivo at the site of administration; mice impaired in MV shedding were protected from EAE, suggesting a pathogenic role for MVs in the disease. Finally, FTY720, the first approved oral MS drug, significantly reduced the amount of MVs in the CSF of EAE-treated mice. Interpretation: These findings identify myeloid MVs as a marker and therapeutic target of brain inflammation. ANN NEUROL 2012;72:610-624

Original languageEnglish
Pages (from-to)610-624
Number of pages15
JournalAnnals of Neurology
Volume72
Issue number4
DOIs
Publication statusPublished - Oct 2012

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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    Verderio, C., Muzio, L., Turola, E., Bergami, A., Novellino, L., Ruffini, F., Riganti, L., Corradini, I., Francolini, M., Garzetti, L., Maiorino, C., Servida, F., Vercelli, A., Rocca, M., Libera, D. D., Martinelli, V., Comi, G., Martino, G., Matteoli, M., & Furlan, R. (2012). Myeloid microvesicles are a marker and therapeutic target for neuroinflammation. Annals of Neurology, 72(4), 610-624. https://doi.org/10.1002/ana.23627