NDLI: The P2X7 receptor and Pannexin-1 are both required for the promotion of multinucleated macrophages by the inflammatory cytokine GM-CSF.

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The P2X7 receptor and Pannexin-1 are both required for the promotion of multinucleated macrophages by the inflammatory cytokine GM-CSF.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Lemaire, Irma Pellegatti, Patrizia Zhang, Bin Di Virgilio, Francesco Falzoni, Simonetta
Description	Country affiliation: Canada Author Affiliation: Lemaire I ( Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada. ilemaire@uottawa.ca)
Abstract	The P2X(7) receptor (P2X(7)R), an ATP-gated ion channel, has been implicated in the process of cell-to-cell fusion into multinucleated macrophages (MA), but its contribution to MA fusion driven by physiological/pathological stimuli is not clearly established. Based on several lines of evidence, we demonstrate that P2X(7)R is critical for the induction of multinucleated MA by the inflammatory cytokine GM-CSF: 1) pharmacological inhibition of P2X(7)R with oxidized ATP (oATP), KN-62, and the selective antagonist A740003 abrogated GM-CSF action on rat alveolar MA and murine peritoneal MA; 2) a murine J774 P2X(7) low MA clone, selected for defective P2X(7)R function, was unresponsive; 3) MA from mice lacking P2X(7)R failed to respond to GM-CSF, in contrast to wild-type. GM-CSF also stimulated ATP-induced membrane permeabilization in J774 P2X(7) high MA and rat alveolar MA, an effect absent in the P2X(7) low MA clone and inhibited by the P2X(7) blockers oATP and KN-62. Notably, the stimulatory effects of GM-CSF on pore formation and MA fusion were both inhibited by blocking functional Pannexin-1 (Panx-1), and GM-CSF failed to stimulate MA fusion in cells from Panx-1 knockout mice. We provide further evidence that extracellular ATP release from peritoneal MA is dependent on P2X(7) but not on Panx-1 expression and that its metabolism to adenosine mediates P2X(7)-dependent MA fusion. These data demonstrate that both P2X(7) and Panx-1 are required for GM-CSF promotion of MA fusion but likely act independently through different signaling pathway(s).
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	7
Volume Number	187
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2011-10-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Connexins Immunology Giant Cells Granulocyte-macrophage Colony-stimulating Factor Macrophages Nerve Tissue Proteins Receptors, Purinergic P2x7 Animals Blotting, Western Metabolism Cytology Hek293 Cells Mice Mice, Inbred C57bl Mice, Knockout Polymerase Chain Reaction Rats, Wistar Signal Transduction Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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The P2X7 receptor and Pannexin-1 are both required for the promotion of multinucleated macrophages by the inflammatory cytokine GM-CSF.

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