In:
The Journal of Immunology, The American Association of Immunologists, Vol. 182, No. 7 ( 2009-04-01), p. 4378-4385
Abstract:
Extracellular ATP is a mediator of intercellular communication and a danger signal. Release of this and other nucleotides modulates microglia responses via P2Y and P2X receptors, among which the P2X7 subtype stands out for its proinflammatory activity and for up-regulation in a transgenic model of Alzheimer disease and in brains from Alzheimer disease patients. Here we show that amyloid β (Aβ) triggered increases in intracellular Ca2+ ([Ca2+]i), ATP release, IL-1β secretion, and plasma membrane permeabilization in microglia from wild-type but not from P2X7-deleted mice. Likewise, intra-hippocampal injection of Aβ caused a large accumulation of IL-1β in wild-type but not in P2X7−/− mice. These observations suggest that Aβ activates a purinergic autocrine/paracrine stimulatory loop of which the P2X7 receptor is an obligate component. Identification of the P2X7 receptor as a non-dispensable factor of Aβ-mediated microglia stimulation may open new avenues for the treatment of Alzheimer disease.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.0803612
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2009
detail.hit.zdb_id:
1475085-5
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