J. Cell Biol.
© The Rockefeller University Press
0021-9525/97/08/697/10 $2.00
Volume 138, Number 3, August 11, 1997 697-706

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 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.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Qu, Y., Franchi, L., Nunez, G., Dubyak, G. R. (2007). Nonclassical IL-1beta Secretion Stimulated by P2X7 Receptors Is Dependent on Inflammasome Activation and Correlated with Exosome Release in Murine Macrophages. J. Immunol. 179: 1913-1925 [Abstract] [Full Text]  
• Lemaire, I., Falzoni, S., Leduc, N., Zhang, B., Pellegatti, P., Adinolfi, E., Chiozzi, P., Di Virgilio, F. (2006). Involvement of the Purinergic P2X7 Receptor in the Formation of Multinucleated Giant Cells. J. Immunol. 177: 7257-7265 [Abstract] [Full Text]  
• Chen, L., Brosnan, C. F. (2006). Exacerbation of Experimental Autoimmune Encephalomyelitis in P2X7R-/- Mice: Evidence for Loss of Apoptotic Activity in Lymphocytes.. J. Immunol. 176: 3115-3126 [Abstract] [Full Text]  
• Raffaghello, L., Chiozzi, P., Falzoni, S., Di Virgilio, F., Pistoia, V. (2006). The P2X7 Receptor Sustains the Growth of Human Neuroblastoma Cells through a Substance P-Dependent Mechanism. Cancer Res. 66: 907-914 [Abstract] [Full Text]  
• Mackenzie, A. B., Young, M. T., Adinolfi, E., Surprenant, A. (2005). Pseudoapoptosis Induced by Brief Activation of ATP-gated P2X7 Receptors. J. Biol. Chem. 280: 33968-33976 [Abstract] [Full Text]  
• Auger, R., Motta, I., Benihoud, K., Ojcius, D. M., Kanellopoulos, J. M. (2005). A Role for Mitogen-activated Protein KinaseErk1/2 Activation and Non-selective Pore Formation in P2X7 Receptor-mediated Thymocyte Death. J. Biol. Chem. 280: 28142-28151 [Abstract] [Full Text]  
• Tsukimoto, M., Harada, H., Ikari, A., Takagi, K. (2005). Involvement of Chloride in Apoptotic Cell Death Induced by Activation of ATP-sensitive P2X7 Purinoceptor. J. Biol. Chem. 280: 2653-2658 [Abstract] [Full Text]  
• Fortes, F. S. A., Pecora, I. L., Persechini, P. M., Hurtado, S., Costa, V., Coutinho-Silva, R., Braga, M. B. M., Silva-Filho, F. C., Bisaggio, R. C., de Farias, F. P., Scemes, E., de Carvalho, A. C. C., Goldenberg, R. C. S. (2004). Modulation of intercellular communication in macrophages: possible interactions between GAP junctions and P2 receptors. J. Cell Sci. 117: 4717-4726 [Abstract] [Full Text]  
• Hiken, J. F., Steinberg, T. H. (2004). ATP downregulates P2X7 and inhibits osteoclast formation in RAW cells. Am. J. Physiol. Cell Physiol. 287: C403-C412 [Abstract] [Full Text]  
• Pfeiffer, Z. A., Aga, M., Prabhu, U., Watters, J. J., Hall, D. J., Bertics, P. J. (2004). The nucleotide receptor P2X7 mediates actin reorganization and membrane blebbing in RAW 264.7 macrophages via p38 MAP kinase and Rho. J. Leukoc. Biol. 75: 1173-1182 [Abstract] [Full Text]  
• Raouf, R., Chakfe, Y., Blais, D., Speelman, A., Boue-Grabot, E., Henderson, D., Seguela, P. (2004). Selective Knock-Down of P2X7 ATP Receptor Function by Dominant-Negative Subunits. Mol. Pharmacol. 65: 646-654 [Abstract] [Full Text]  
• Adinolfi, E., Kim, M., Young, M. T., Di Virgilio, F., Surprenant, A. (2003). Tyrosine Phosphorylation of HSP90 within the P2X7 Receptor Complex Negatively Regulates P2X7 Receptors. J. Biol. Chem. 278: 37344-37351 [Abstract] [Full Text]  
• Ke, H. Z., Qi, H., Weidema, A. F., Zhang, Q., Panupinthu, N., Crawford, D. T., Grasser, W. A., Paralkar, V. M., Li, M., Audoly, L. P., Gabel, C. A., Jee, W. S. S., Dixon, S. J., Sims, S. M., Thompson, D. D. (2003). Deletion of the P2X7 Nucleotide Receptor Reveals Its Regulatory Roles in Bone Formation and Resorption. Mol. Endocrinol. 17: 1356-1367 [Abstract] [Full Text]  
• Eugenin, E. A., Branes, M. C., Berman, J. W., Saez, J. C. (2003). TNF-{alpha} Plus IFN-{gamma} Induce Connexin43 Expression and Formation of Gap Junctions Between Human Monocytes/Macrophages That Enhance Physiological Responses. J. Immunol. 170: 1320-1328 [Abstract] [Full Text]  
• North, R. A. (2002). Molecular Physiology of P2X Receptors. Physiol. Rev. 82: 1013-1067 [Abstract] [Full Text]  
• Smart, M. L., Panchal, R. G., Bowser, D. N., Williams, D. A., Petrou, S. (2002). Pore formation is not associated with macroscopic redistribution of P2X7 receptors. Am. J. Physiol. Cell Physiol. 283: C77-C84 [Abstract] [Full Text]  
• Labasi, J. M., Petrushova, N., Donovan, C., McCurdy, S., Lira, P., Payette, M. M., Brissette, W., Wicks, J. R., Audoly, L., Gabel, C. A. (2002). Absence of the P2X7 Receptor Alters Leukocyte Function and Attenuates an Inflammatory Response. J. Immunol. 168: 6436-6445 [Abstract] [Full Text]  
• Weidema, A. F., Dixon, S. J., Sims, S. M. (2001). Activation of P2Y but not P2X4 nucleotide receptors causes elevation of [Ca2+]i in mammalian osteoclasts. Am. J. Physiol. Cell Physiol. 280: C1531-C1539 [Abstract] [Full Text]  
• Stober, C. B., Lammas, D. A., Li, C. M., Kumararatne, D. S., Lightman, S. L., McArdle, C. A. (2001). ATP-Mediated Killing of Mycobacterium bovis Bacille Calmette-Guerin Within Human Macrophages Is Calcium Dependent and Associated with the Acidification of Mycobacteria-Containing Phagosomes. J. Immunol. 166: 6276-6286 [Abstract] [Full Text]  
• Gudipaty, L., Humphreys, B. D., Buell, G., Dubyak, G. R. (2001). Regulation of P2X7 nucleotide receptor function in human monocytes by extracellular ions and receptor density. Am. J. Physiol. Cell Physiol. 280: C943-C953 [Abstract] [Full Text]  
• Eugenín, E. A., Eckardt, D., Theis, M., Willecke, K., Bennett, M. V. L., Sáez, J. C. (2001). Microglia at brain stab wounds express connexin 43 and in vitro form functional gap junctions after treatment with interferon-gamma and tumor necrosis factor-alpha. Proc. Natl. Acad. Sci. USA 10.1073/pnas.051634298v1 [Abstract] [Full Text]  
• Di Virgilio, F., Chiozzi, P., Ferrari, D., Falzoni, S., Sanz, J. M., Morelli, A., Torboli, M., Bolognesi, G., Baricordi, O. R. (2001). Nucleotide receptors: an emerging family of regulatory molecules in blood cells. Blood 97: 587-600 [Abstract] [Full Text]  
• Falzoni, S., Chiozzi, P., Ferrari, D., Buell, G., Di Virgilio, F. (2000). P2X7 Receptor and Polykarion Formation. Mol. Biol. Cell 11: 3169-3176 [Abstract] [Full Text]  
• Nihei, O. K., de Carvalho, A. C. C., Savino, W., Alves, L. A. (2000). Pharmacologic properties of P2Z/P2X7 receptor characterized in murine dendritic cells: role on the induction of apoptosis. Blood 96: 996-1005 [Abstract] [Full Text]  
• Mutini, C., Falzoni, S., Ferrari, D., Chiozzi, P., Morelli, A., Baricordi, O. R., Collo, G., Ricciardi-Castagnoli, P., Di Virgilio, F. (1999). Mouse Dendritic Cells Express the P2X7 Purinergic Receptor: Characterization and Possible Participation in Antigen Presentation. J. Immunol. 163: 1958-1965 [Abstract] [Full Text]  
• Ferrari, D., Stroh, C., Schulze-Osthoff, K. (1999). P2X7/P2Z Purinoreceptor-mediated Activation of Transcription Factor NFAT in Microglial Cells. J. Biol. Chem. 274: 13205-13210 [Abstract] [Full Text]  
• Coutinho-Silva, R., Persechini, P. M., Bisaggio, R. D. C., Perfettini, J.-L., Neto, A. C. T. D. S., Kanellopoulos, J. M., Motta-Ly, I., Dautry-Varsat, A., Ojcius, D. M. (1999). P2Z/P2X7 receptor-dependent apoptosis of dendritic cells. Am. J. Physiol. Cell Physiol. 276: C1139-C1147 [Abstract] [Full Text]  
• Schulze-Lohoff, E., Hugo, C., Rost, S., Arnold, S., Gruber, A., Brune, B., Sterzel, R. B. (1998). Extracellular ATP causes apoptosis and necrosis of cultured mesangial cells via P2Z/P2X7 receptors. Am. J. Physiol. Renal Physiol. 275: F962-F971 [Abstract] [Full Text]  
• Buell, G., Chessell, I.P., Michel, A.D., Collo, G., Salazzo, M., Herren, S., Gretener, D., Grahames, C., Kaur, R., Kosco-Vilbois, M.H., Humphrey, P.P.A. (1998). Blockade of Human P2X7 Receptor Function With a Monoclonal Antibody. Blood 92: 3521-3528 [Abstract] [Full Text]  
• Alzola, E., Perez-Etxebarria, A., Kabre, E., Fogarty, D. J., Metioui, M., Chaib, N., Macarulla, J. M., Matute, C., Dehaye, J.-P., Marino, A. (1998). Activation by P2X7 Agonists of Two Phospholipases A2 (PLA2) in Ductal Cells of Rat Submandibular Gland. COUPLING OF THE CALCIUM-INDEPENDENT PLA2 WITH KALLIKREIN SECRETION. J. Biol. Chem. 273: 30208-30217 [Abstract] [Full Text]  
• Sterling, H., Saginario, C., Vignery, A. (1998). CD44 Occupancy Prevents Macrophage Multinucleation. J. Cell Biol. 143: 837-847 [Abstract] [Full Text]  
• Saginario, C., Sterling, H., Beckers, C., Kobayashi, R., Solimena, M., Ullu, E., Vignery, A. (1998). MFR, a Putative Receptor Mediating the Fusion of Macrophages. Mol. Cell. Biol. 18: 6213-6223 [Abstract] [Full Text]  
• Tenneti, L., Gibbons, S. J., Talamo, B. R. (1998). Expression and Trans-synaptic Regulation of P2x4 and P2z Receptors for Extracellular ATP in Parotid Acinar Cells. EFFECTS OF PARASYMPATHETIC DENERVATION. J. Biol. Chem. 273: 26799-26808 [Abstract] [Full Text]  
• Ralevic, V., Burnstock, G. (1998). Receptors for Purines and Pyrimidines. Pharmacol. Rev. 50: 413-492 [Abstract] [Full Text]  
• Solle, M., Labasi, J., Perregaux, D. G., Stam, E., Petrushova, N., Koller, B. H., Griffiths, R. J., Gabel, C. A. (2001). Altered Cytokine Production in Mice Lacking P2X7 Receptors. J. Biol. Chem. 276: 125-132 [Abstract] [Full Text]  
• Eugenin, E. A., Eckardt, D., Theis, M., Willecke, K., Bennett, M. V. L., Saez, J. C. (2001). Microglia at brain stab wounds express connexin 43 and in vitro form functional gap junctions after treatment with interferon-gamma and tumor necrosis factor-alpha. Proc. Natl. Acad. Sci. USA 98: 4190-4195 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents