| NTPDase1 governs P2X7-dependent functions in murine macrophages. | |
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MedLine Citation:
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PMID: 20201036 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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P2X7 receptor is an adenosine triphosphate (ATP)-gated ion channel within the multiprotein inflammasome complex. Until now, little is known about regulation of P2X7 effector functions in macrophages. In this study, we show that nucleoside triphosphate diphosphohydrolase 1 (NTPDase1)/CD39 is the dominant ectonucleotidase expressed by murine peritoneal macrophages and that it regulates P2X7-dependent responses in these cells. Macrophages isolated from NTPDase1-null mice (Entpd1(-/-)) were devoid of all ADPase and most ATPase activities when compared with WT macrophages (Entpd1(+/+)). Entpd1(-/-) macrophages exposed to millimolar concentrations of ATP were more susceptible to cell death, released more IL-1beta and IL-18 after TLR2 or TLR4 priming, and incorporated the fluorescent dye Yo-Pro-1 more efficiently (suggestive of increased pore formation) than Entpd1(+/+) cells. Consistent with these observations, NTPDase1 regulated P2X7-associated IL-1beta release after synthesis, and this process occurred independently of, and prior to, cytokine maturation by caspase-1. NTPDase1 also inhibited IL-1beta release in vivo in the air pouch inflammatory model. Exudates of LPS-injected Entpd1(-/-) mice had significantly higher IL-1beta levels when compared with Entpd1(+/+) mice. Altogether, our studies suggest that NTPDase1/CD39 plays a key role in the control of P2X7-dependent macrophage responses. |
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Authors:
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Sébastien A Lévesque; Filip Kukulski; Keiichi Enjyoji; Simon C Robson; Jean Sévigny |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: European journal of immunology Volume: 40 ISSN: 1521-4141 ISO Abbreviation: Eur. J. Immunol. Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-05-04 Completed Date: 2010-06-17 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 1273201 Medline TA: Eur J Immunol Country: Germany |
Other Details:
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Languages: eng Pagination: 1473-85 Citation Subset: IM |
Affiliation:
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Centre de Recherche en Rhumatologie et Immunologie, Centre Hospitalier Universitaire de Québec, Université Laval, Québec, QC, Canada. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine Triphosphate
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metabolism Animals Antigens, CD / genetics, physiology* Apoptosis / physiology Apyrase / deficiency, genetics, physiology* Bone Marrow Cells / enzymology, secretion Caspases / physiology Cell Membrane Permeability Crosses, Genetic Cysteine Proteinase Inhibitors / pharmacology Interleukin-1beta / secretion Macrophages, Peritoneal / enzymology*, secretion Mice Mice, Inbred C57BL Mice, Knockout Receptors, Purinergic P2 / physiology* Receptors, Purinergic P2X7 Toll-Like Receptor 2 / physiology |
| Grant Support | |
ID/Acronym/Agency:
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67520//Canadian Institutes of Health Research; 68957//Canadian Institutes of Health Research; 93683//Canadian Institutes of Health Research; HL094400/HL/NHLBI NIH HHS; R01 HL094400-01/HL/NHLBI NIH HHS; //Canadian Institutes of Health Research |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD; 0/Cysteine Proteinase Inhibitors; 0/Interleukin-1beta; 0/P2rx7 protein, mouse; 0/Receptors, Purinergic P2; 0/Receptors, Purinergic P2X7; 0/Tlr2 protein, mouse; 0/Toll-Like Receptor 2; 56-65-5/Adenosine Triphosphate; EC 3.4.22.-/Caspases; EC 3.6.1.5/Apyrase; EC 3.6.1.5/CD39 antigen |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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