Premium
Acid sphingomyelinase activity triggers microparticle release from glial cells
Author(s) -
Bianco Fabio,
Perrotta Cristiana,
Novellino Luisa,
Francolini Maura,
Riganti Loredana,
Menna Elisabetta,
Saglietti Laura,
Schuchman Edward H,
Furlan Roberto,
Clementi Emilio,
Matteoli Michela,
Verderio Claudia
Publication year - 2009
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2009.45
Subject(s) - acid sphingomyelinase , microparticle , sphingomyelin , microbiology and biotechnology , biology , exocytosis , biochemistry , biophysics , membrane , astrobiology
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‐1β, 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‐1β 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‐1β 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‐1β release, thus, opening new strategies for the treatment of neuroinflammatory diseases.