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Spontaneous cell fusion in macrophage cultures expressing high levels of the P2Z/P2X7 receptor.

Chiozzi P, Sanz JM, Ferrari D, Falzoni S, Aleotti A, Buell GN, Collo G, Di Virgilio F - J. Cell Biol. (1997)

Bottom Line: Clin.Invest. 95:1207- 1216).These observations support our previous hypothesis that the P2Z/P2X7 receptor is involved in macrophage fusion.

View Article: PubMed Central - PubMed

Affiliation: Institute of General Pathology, University of Ferrara, I-44100 Ferrara, Italy.

ABSTRACT
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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Early cellular interactions in cultures of P2Zhyper macrophages. Experimental conditions as in Fig. 5.
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Figure 8: Early cellular interactions in cultures of P2Zhyper macrophages. Experimental conditions as in Fig. 5.

Mentions: P2Zhyper macrophages formed cell aggregates that preceeded fusion. It was very common to find within such aggregates, images suggestive of initial cytoplasmic communication between adjacent cells (Fig. 8, A and B, arrows). Most often, an already-formed MGC was itself a center of aggregation to which other cells were attracted up to the eventual fusion (Fig. 8 C). We examined some of these aggregates by transmission electron microscopy. As shown in Fig. 9, there were sites of close apposition between membranes of adjacent cells, and sometimes the juxtaposed plasma membranes were about to fuse (Fig. 9, arrows).


Spontaneous cell fusion in macrophage cultures expressing high levels of the P2Z/P2X7 receptor.

Chiozzi P, Sanz JM, Ferrari D, Falzoni S, Aleotti A, Buell GN, Collo G, Di Virgilio F - J. Cell Biol. (1997)

Early cellular interactions in cultures of P2Zhyper macrophages. Experimental conditions as in Fig. 5.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2141639&req=5

Figure 8: Early cellular interactions in cultures of P2Zhyper macrophages. Experimental conditions as in Fig. 5.
Mentions: P2Zhyper macrophages formed cell aggregates that preceeded fusion. It was very common to find within such aggregates, images suggestive of initial cytoplasmic communication between adjacent cells (Fig. 8, A and B, arrows). Most often, an already-formed MGC was itself a center of aggregation to which other cells were attracted up to the eventual fusion (Fig. 8 C). We examined some of these aggregates by transmission electron microscopy. As shown in Fig. 9, there were sites of close apposition between membranes of adjacent cells, and sometimes the juxtaposed plasma membranes were about to fuse (Fig. 9, arrows).

Bottom Line: Clin.Invest. 95:1207- 1216).These observations support our previous hypothesis that the P2Z/P2X7 receptor is involved in macrophage fusion.

View Article: PubMed Central - PubMed

Affiliation: Institute of General Pathology, University of Ferrara, I-44100 Ferrara, Italy.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus