Acid sphingomyelinase activity triggers microparticle release from glial cells. (Articolo in rivista)

Type
Label
  • Acid sphingomyelinase activity triggers microparticle release from glial cells. (Articolo in rivista) (literal)
Anno
  • 2009-01-01T00:00:00+01:00 (literal)
Alternative label
  • Bianco F, Perrotta C., Novellino L., Francolini M, Riganti L, Menna E, Taglietti L, Schuchman EH, Furlan R, Clementi E , Matteoli M and Verderio C (2009)
    Acid sphingomyelinase activity triggers microparticle release from glial cells.
    in EMBO journal (Print)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Bianco F, Perrotta C., Novellino L., Francolini M, Riganti L, Menna E, Taglietti L, Schuchman EH, Furlan R, Clementi E , Matteoli M and Verderio C (literal)
Pagina inizio
  • 1043 (literal)
Pagina fine
  • 1054 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 28 (literal)
Rivista
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • 1. Univ Milan, Inst Neurosci, Dept Med Pharmacol, CNR, I-20129 Milan, Italy 2. NeuroZone Srl, Milan, Italy 3. Hosp Luigi Sacco, Milan, Italy 4. Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA 5. Ist Sci San Raffaele, Clin Neuroimmunol Unit, Inst Expt Neurol, I-20132 Milan, Italy 6. Medea Sci Inst, Bosisio Parini, Italy 7. LITA Vialba Univ Milano, Dept Preclin Sci, Milan, Italy 8. Fdn Don C Gnocchi, Milan, Italy (literal)
Titolo
  • Acid sphingomyelinase activity triggers microparticle release from glial cells. (literal)
Abstract
  • We have earlier shown that microglia, the immune cells of the CNS, release microparticles from cell plasma membrane after ATP stimulation. These vesicles contain and release IL-1 beta, a crucial cytokine in CNS inflammatory events. In this study, we show that microparticles are also released by astrocytes and we get insights into the mechanism of their shedding. We show that, on activation of the ATP receptor P2X(7), microparticle shedding is associated with rapid activation of acid sphingomyelinase, which moves to plasma membrane outer leaflet. ATP-induced shedding and IL-1 beta release are markedly reduced by the inhibition of acid sphingomyelinase, and completely blocked in glial cultures from acid sphingomyelinase knockout mice. We also show that p38 MAPK cascade is relevant for the whole process, as specific kinase inhibitors strongly reduce acid sphingomyelinase activation, microparticle shedding and IL-1 beta release. Our results represent the first demonstration that activation of acid sphingomyelinase is necessary and sufficient for microparticle release from glial cells and define key molecular effectors of microparticle formation and IL-1 beta release, thus, opening new strategies for the treatment of neuroinflammatory diseases. (literal)
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