Spontaneous Cell Fusion in Macrophage Cultures Expressing High Levels of the P2Z/P2X7 Receptor

doi:10.1083/jcb.138.3.697

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© The Rockefeller University Press, 0021-9525/1997//697 $5.00
The Journal of Cell Biology, Volume 138, Number 3, , 1997 697-706

Article

Spontaneous Cell Fusion in Macrophage Cultures Expressing High Levels of the P2Z/P2X₇ Receptor

Paola Chiozzi^*, Juana M. Sanz^*, Davide Ferrari^*, Simonetta Falzoni^*, Arrigo Aleotti, Gary N. Buell^||, Ginetta Collo^||, and 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

Mouse and human macrophages express a plasma membrane receptorfor extracellular ATP named P2Z/P2X₇. This molecule, recentlycloned, is endowed with the intriguing property of forming anaqueous pore that allows transmembrane fluxes of hydrophylicmolecules of molecular weight below 900. The physiologicalfunction of this receptor is unknown. In a previous study wereported experiments suggesting that the P2Z/P2X₇ receptoris involved in the formation of macrophage-derived multinucleatedgiant 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 mouseJ774 macrophages that are characterized by either high or low expression of the P2Z/P2X₇ receptor and named these clonesP2Zhyper or P2Zhypo, respectively. P2Zhyper, but not P2Zhypo,cells grown to confluence in culture spontaneously fuse toform MGCs. As previously shown for human macrophages, fusionis inhibited by the P2Z/P2X₇ blocker oxidized ATP. MGCs die shortly after fusion through a dramatic process of cytoplasmicsepimentation followed by fragmentation. These observationssupport our previous hypothesis that the P2Z/P2X₇ receptoris involved in macrophage fusion.

Abbreviations used in this paper: IFN- ${gamma}$ , interferon- ${gamma}$ ; MGC, multinucleated giant cells.

The help of Dr. Sybille Neidhart is gratefully acknowledged.We also thank Dr. Annmarie Surprenant for the kind gift ofHEK293 cells stably transfected with P2X₂ cDNA.

Please address all correspondence to Dr. Francesco Di Virgilio,Institute of General Pathology, University of Ferrara, ViaBorsari, 4, I-44100 Ferrara, Italy. Tel.:(39)532-291-353; Fax:(39)532-247-278;E-mail: fdv{at}ifeuniv.unife.it

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