Format

Send to

Choose Destination
EMBO J. 2009 Apr 22;28(8):1043-54. doi: 10.1038/emboj.2009.45. Epub 2009 Mar 19.

Acid sphingomyelinase activity triggers microparticle release from glial cells.

Author information

1
CNR Institute of Neuroscience and Department of Medical Pharmacology, University of Milano, Milano, Italy.

Erratum in

  • EMBO J. 2009 May 6;28(9):1374.

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-1beta, 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 P2X7, microparticle shedding is associated with rapid activation of acid sphingomyelinase, which moves to plasma membrane outer leaflet. ATP-induced shedding and IL-1beta 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-1beta 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-1beta release, thus, opening new strategies for the treatment of neuroinflammatory diseases.

PMID:
19300439
PMCID:
PMC2664656
DOI:
10.1038/emboj.2009.45
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center