1. Myeloid microvesicles are a marker and therapeutic target for neuroinflammation
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Francesca Ruffini, Chiara Maiorino, Luisa Novellino, Alessandro Vercelli, Michela Matteoli, Federica Servida, Claudia Verderio, Loredana Riganti, Gianvito Martino, Livia Garzetti, Elena Turola, M A Rocca, Irene Corradini, Giancarlo Comi, Alessandra Bergami, Vittorio Martinelli, Roberto Furlan, Dacia Dalla Libera, Luca Muzio, Maura Francolini, 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, DALLA LIBERA, D, Martinelli, V, Comi, G, Martino, Gianvito, Matteoli, M, and Furlan, R.
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Pathology ,Myeloid ,Cell Communication ,Nervous System Autoimmune Disease, Experimental ,neuroinflammation ,Rats, Sprague-Dawley ,Mice ,0302 clinical medicine ,Central Nervous System Diseases ,acid sphingomyelinase ,Cells, Cultured ,Mice, Knockout ,0303 health sciences ,Microglia ,Experimental autoimmune encephalomyelitis ,microvesicles ,Flow Cytometry ,3. Good health ,medicine.anatomical_structure ,Sphingomyelin Phosphodiesterase ,Neurology ,Spinal Cord ,Encephalitis ,medicine.symptom ,Neuroglia ,medicine.medical_specialty ,Multiple Sclerosis ,Blotting, Western ,Inflammation ,Biology ,Real-Time Polymerase Chain Reaction ,03 medical and health sciences ,In vivo ,medicine ,Animals ,Calcium Signaling ,Neuroinflammation ,030304 developmental biology ,Multiple sclerosis ,Lentivirus ,medicine.disease ,Microvesicles ,Rats ,Mice, Inbred C57BL ,Microscopy, Electron ,Microscopy, Fluorescence ,Rats, Inbred Lew ,Immunology ,Neurology (clinical) ,030217 neurology & neurosurgery ,Biomarkers - 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;72:610โ624
- Published
- 2012
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