Myeloid microvesicles are a marker and therapeutic target for neuroinflammation
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
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EVs isolated under short ATP stimulation are negative for apoptotic markers and are not contaminated by intracellular organelles derived from damaged cells.
“Our previous evidence indicates that EVs isolated under short ATP stimulation are negative for apoptotic markers and are not contaminated by intracellular organelles derived from damaged cells, as indicated by electron microscopy [6, 78] and western blot analysis [29].”
From Glia-to-neuron transfer of miRNAs via extracellular vesicles: a new mechanism underlying inflammation-induced synaptic alterations (2018) · cites this paper as [78]
Successful polarization of microglia towards inflammatory or pro-regenerative phenotype under the used conditions was confirmed.
“Successful polarization towards inflammatory or pro-regenerative phenotype under these conditions was confirmed (data not shown), according to previous studies”
From Glia-to-neuron transfer of miRNAs via extracellular vesicles: a new mechanism underlying inflammation-induced synaptic alterations (2018) · cites this paper as [78]
Multiple sclerosis (MS) is a synaptic disorder characterized by chronic microglia activation and enhanced EV secretion with early onset compared to other neurodegenerative diseases.
“Multiple sclerosis (MS) is a synaptic disorder characterized by chronic microglia activation and enhanced EV secretion [78] with early onset compared to other neurodegenerative diseases.”
From Glia-to-neuron transfer of miRNAs via extracellular vesicles: a new mechanism underlying inflammation-induced synaptic alterations (2018) · cites this paper as [78]
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- Authors
- 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.
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2012-10
- Volume
- 72
- Issue
- 4
- Pages
- 610-624
- ISSN
- 0364-5134
- 1531-8249
- Cited by
- 299
- References
- 7
- Language
- en
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