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Myeloid microvesicles are a marker and therapeutic target for neuroinflammation
Author(s) -
Verderio Claudia,
Muzio Luca,
Turola Elena,
Bergami Alessandra,
Novellino Luisa,
Ruffini Francesca,
Riganti Loredana,
Corradini Irene,
Francolini Maura,
Garzetti Livia,
Maiorino Chiara,
Servida Federica,
Vercelli Alessandro,
Rocca Mara,
Libera Dacia Dalla,
Martinelli Vittorio,
Comi Giancarlo,
Martino Gianvito,
Matteoli Michela,
Furlan Roberto
Publication year - 2012
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.23627
Subject(s) - microvesicles , multiple sclerosis , neuroinflammation , myeloid , immunology , microglia , encephalomyelitis , experimental autoimmune encephalomyelitis , flow cytometry , cerebrospinal fluid , medicine , inflammation , in vivo , pathology , biology , microrna , biochemistry , microbiology and biotechnology , gene
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