Mouse and human macrophages express a plasma membrane receptor for extracellular ATP named P2Z/P2X7. This molecule, recently cloned, is endowed with the intriguing property of forming an aqueous pore that allows transmembrane fluxes of hydrophylic molecules of molecular weight below 900. The physiological function of this receptor is unknown. In a previous study we reported experiments suggesting that the P2Z/P2X7 receptor is involved in the formation of macrophage-derived multinucleated giant cells (MGCs; Falzoni, S., M. Munerati, D. Ferrari, S. Spisani, S. Moretti, and F. Di Virgilio. 1995. J. Clin. Invest. 95:1207– 1216). We have selected several clones of mouse J774 macrophages that are characterized by either high or low expression of the P2Z/P2X7 receptor and named these clones P2Zhyper or P2Zhypo, respectively. P2Zhyper, but not P2Zhypo, cells grown to confluence in culture spontaneously fuse to form MGCs. As previously shown for human macrophages, fusion is inhibited by the P2Z/P2X7 blocker oxidized ATP. MGCs die shortly after fusion through a dramatic process of cytoplasmic sepimentation followed by fragmentation. These observations support our previous hypothesis that the P2Z/P2X7 receptor is involved in macrophage fusion.
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11 August 1997
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August 11 1997
Spontaneous Cell Fusion in Macrophage Cultures Expressing High Levels of the P2Z/P2X7 Receptor
Paola Chiozzi,
Paola Chiozzi
*Institute of General Pathology, ‡Center of Electron Microscopy, and §Center of Biotechnology, University of Ferrara, I-44100 Ferrara, Italy; and ‖Glaxo-Wellcome Geneva Biomedical Research Institute, 1228 Plan-Les-Ouates, Switzerland
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Juana M. Sanz,
Juana M. Sanz
*Institute of General Pathology, ‡Center of Electron Microscopy, and §Center of Biotechnology, University of Ferrara, I-44100 Ferrara, Italy; and ‖Glaxo-Wellcome Geneva Biomedical Research Institute, 1228 Plan-Les-Ouates, Switzerland
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Davide Ferrari,
Davide Ferrari
*Institute of General Pathology, ‡Center of Electron Microscopy, and §Center of Biotechnology, University of Ferrara, I-44100 Ferrara, Italy; and ‖Glaxo-Wellcome Geneva Biomedical Research Institute, 1228 Plan-Les-Ouates, Switzerland
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Simonetta Falzoni,
Simonetta Falzoni
*Institute of General Pathology, ‡Center of Electron Microscopy, and §Center of Biotechnology, University of Ferrara, I-44100 Ferrara, Italy; and ‖Glaxo-Wellcome Geneva Biomedical Research Institute, 1228 Plan-Les-Ouates, Switzerland
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Arrigo Aleotti,
Arrigo Aleotti
*Institute of General Pathology, ‡Center of Electron Microscopy, and §Center of Biotechnology, University of Ferrara, I-44100 Ferrara, Italy; and ‖Glaxo-Wellcome Geneva Biomedical Research Institute, 1228 Plan-Les-Ouates, Switzerland
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Gary N. Buell,
Gary N. Buell
*Institute of General Pathology, ‡Center of Electron Microscopy, and §Center of Biotechnology, University of Ferrara, I-44100 Ferrara, Italy; and ‖Glaxo-Wellcome Geneva Biomedical Research Institute, 1228 Plan-Les-Ouates, Switzerland
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Ginetta Collo,
Ginetta Collo
*Institute of General Pathology, ‡Center of Electron Microscopy, and §Center of Biotechnology, University of Ferrara, I-44100 Ferrara, Italy; and ‖Glaxo-Wellcome Geneva Biomedical Research Institute, 1228 Plan-Les-Ouates, Switzerland
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Francesco Di Virgilio
Francesco Di Virgilio
*Institute of General Pathology, ‡Center of Electron Microscopy, and §Center of Biotechnology, University of Ferrara, I-44100 Ferrara, Italy; and ‖Glaxo-Wellcome Geneva Biomedical Research Institute, 1228 Plan-Les-Ouates, Switzerland
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Paola Chiozzi
*Institute of General Pathology, ‡Center of Electron Microscopy, and §Center of Biotechnology, University of Ferrara, I-44100 Ferrara, Italy; and ‖Glaxo-Wellcome Geneva Biomedical Research Institute, 1228 Plan-Les-Ouates, Switzerland
Juana M. Sanz
*Institute of General Pathology, ‡Center of Electron Microscopy, and §Center of Biotechnology, University of Ferrara, I-44100 Ferrara, Italy; and ‖Glaxo-Wellcome Geneva Biomedical Research Institute, 1228 Plan-Les-Ouates, Switzerland
Davide Ferrari
*Institute of General Pathology, ‡Center of Electron Microscopy, and §Center of Biotechnology, University of Ferrara, I-44100 Ferrara, Italy; and ‖Glaxo-Wellcome Geneva Biomedical Research Institute, 1228 Plan-Les-Ouates, Switzerland
Simonetta Falzoni
*Institute of General Pathology, ‡Center of Electron Microscopy, and §Center of Biotechnology, University of Ferrara, I-44100 Ferrara, Italy; and ‖Glaxo-Wellcome Geneva Biomedical Research Institute, 1228 Plan-Les-Ouates, Switzerland
Arrigo Aleotti
*Institute of General Pathology, ‡Center of Electron Microscopy, and §Center of Biotechnology, University of Ferrara, I-44100 Ferrara, Italy; and ‖Glaxo-Wellcome Geneva Biomedical Research Institute, 1228 Plan-Les-Ouates, Switzerland
Gary N. Buell
*Institute of General Pathology, ‡Center of Electron Microscopy, and §Center of Biotechnology, University of Ferrara, I-44100 Ferrara, Italy; and ‖Glaxo-Wellcome Geneva Biomedical Research Institute, 1228 Plan-Les-Ouates, Switzerland
Ginetta Collo
*Institute of General Pathology, ‡Center of Electron Microscopy, and §Center of Biotechnology, University of Ferrara, I-44100 Ferrara, Italy; and ‖Glaxo-Wellcome Geneva Biomedical Research Institute, 1228 Plan-Les-Ouates, Switzerland
Francesco Di Virgilio
*Institute of General Pathology, ‡Center of Electron Microscopy, and §Center of Biotechnology, University of Ferrara, I-44100 Ferrara, Italy; and ‖Glaxo-Wellcome Geneva Biomedical Research Institute, 1228 Plan-Les-Ouates, Switzerland
The help of Dr. Sybille Neidhart is gratefully acknowledged. We also thank Dr. Annmarie Surprenant for the kind gift of HEK293 cells stably transfected with P2X2 cDNA.
Please address all correspondence to Dr. Francesco Di Virgilio, Institute of General Pathology, University of Ferrara, Via Borsari, 4, I-44100 Ferrara, Italy. Tel.:(39)532-291-353; Fax:(39)532-247-278; E-mail: [email protected]
Received:
January 14 1997
Revision Received:
June 02 1997
Online ISSN: 1540-8140
Print ISSN: 0021-9525
1997
J Cell Biol (1997) 138 (3): 697–706.
Article history
Received:
January 14 1997
Revision Received:
June 02 1997
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Paola Chiozzi, Juana M. Sanz, Davide Ferrari, Simonetta Falzoni, Arrigo Aleotti, Gary N. Buell, Ginetta Collo, Francesco Di Virgilio; Spontaneous Cell Fusion in Macrophage Cultures Expressing High Levels of the P2Z/P2X7 Receptor . J Cell Biol 11 August 1997; 138 (3): 697–706. doi: https://doi.org/10.1083/jcb.138.3.697
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