title: 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.
  
  
  CONCLUSIONS
  These findings identify myeloid MVs as a marker and therapeutic target of brain inflammation.
authors.affiliation: Italian National Research Council Institute of Neuroscience and Department of Medical Pharmacology, University of Milan, Milan, Italy. c.verderio@in.cnr.it
authors.forename: Claudia
authors.initials: C
authors.lastname: Verderio
authors.forename: Luca
authors.initials: L
authors.lastname: Muzio
authors.forename: Elena
authors.initials: E
authors.lastname: Turola
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bergami
authors.forename: Luisa
authors.initials: L
authors.lastname: Novellino
authors.forename: Francesca
authors.initials: F
authors.lastname: Ruffini
authors.forename: Loredana
authors.initials: L
authors.lastname: Riganti
authors.forename: Irene
authors.initials: I
authors.lastname: Corradini
authors.forename: Maura
authors.initials: M
authors.lastname: Francolini
authors.forename: Livia
authors.initials: L
authors.lastname: Garzetti
authors.forename: Chiara
authors.initials: C
authors.lastname: Maiorino
authors.forename: Federica
authors.initials: F
authors.lastname: Servida
authors.forename: Alessandro
authors.initials: A
authors.lastname: Vercelli
authors.forename: Mara
authors.initials: M
authors.lastname: Rocca
authors.forename: Dacia
authors.initials: D
authors.lastname: Dalla Libera
authors.forename: Vittorio
authors.initials: V
authors.lastname: Martinelli
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Comi
authors.forename: Gianvito
authors.initials: G
authors.lastname: Martino
authors.forename: Michela
authors.initials: M
authors.lastname: Matteoli
authors.forename: Roberto
authors.initials: R
authors.lastname: Furlan
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D015153:Blotting, Western; D020013:Calcium Signaling / Q000502:physiology; D002450:Cell Communication; D002478:Cells, Cultured; D002493:Central Nervous System Diseases / Q000134:cerebrospinal fluid* / Q000188:drug therapy*; D004660:Encephalitis / Q000134:cerebrospinal fluid / Q000473:pathology; D005434:Flow Cytometry; D007249:Inflammation / Q000134:cerebrospinal fluid* / Q000188:drug therapy*; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D009103:Multiple Sclerosis / Q000473:pathology; D020721:Nervous System Autoimmune Disease, Experimental / Q000134:cerebrospinal fluid / Q000188:drug therapy; D009457:Neuroglia / Q000378:metabolism / Q000502:physiology; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D013108:Sphingomyelin Phosphodiesterase / Q000235:genetics / Q000502:physiology; D013116:Spinal Cord / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D013108:Sphingomyelin Phosphodiesterase