| TRANSIENT P2X7 RECEPTOR ACTIVATION TRIGGERS MACROPHAGE DEATH INDEPENDENT OF TLR2/4, CASP1 AND PANX1. | |
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MedLine Citation:
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PMID: 22235111 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The function of P2X7 receptors (ATP-gated ion channels) in innate immune cells is unclear. In the setting of Toll-like receptor (TLR) stimulation, secondary activation of P2X7 ion channels has been linked to pro-caspase-1 cleavage and cell death. Here we show that cell death is a surprisingly early triggered event. We show using live-cell imaging that transient (1-4 min) stimulation of mouse macrophages with high extracellular ATP ([ATP]e) triggers delayed (hours) cell death, indexed as DEVDase (caspase-3 and caspase-7) activity. Continuous or transient high [ATP]e did not induce cell death in P2X7-deficient (P2X7-/-) macrophages or neutrophils (in which P2X7 could not be detected). Blocking sustained Ca2+ influx, a signature of P2X7 ligation, was highly protective, whereas no protection was conferred in macrophages lacking caspase-1 or TLR2 and TLR4. Furthermore, pannexin-1 (Panx1)-deficiency had no effect on transient ATP-induced delayed cell death or ATP-induced Yo-Pro-1 uptake (an index of large pore pathway formation). Thus, transient P2X7 receptor activation and Ca2+ overload act as a death trigger for native mouse macrophages independent of Panx1 and pro-inflammatory caspase-1 and TLR signaling. |
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Authors:
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Peter J Hanley; Moritz Kronlage; Carsten Kirschning; Adriana Del Rey; Francesco Di Virgilio; Jens Leipziger; Iain P Chessell; Sarah Sargin; Mikhail A Filippov; Otto Lindemann; Simon Mohr; Volker Koenigs; Hermann Schillers; Martin Baehler; Albrecht Schwab |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-10 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: - ISSN: 1083-351X ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-11 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Institut fuer Molekulare Zellbiologie, Germany; |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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