P2X7 Receptor and Polykarion Formation

AUTOR(ES)

Falzoni, Simonetta

FONTE

The American Society for Cell Biology

RESUMO

Cell fusion is a central phenomenon during the immune response that leads to formation of large elements called multinucleated giant cells (MGCs) of common occurrence at sites of granulomatous inflammation. We have previously reported on the involvement in this event of a novel receptor expressed to high level by mononuclear phagocytes, the purinergic P2X7 receptor. Herein, we show that blockade of this receptor by a specific monoclonal antibody prevents fusion in vitro. In contrast, cell fusion is stimulated by addition of enzymes that destroy extracellular ATP (i.e., apyrase or hexokinase). Experiments performed with phagocytes selected for high (P2X7 hyper) or low (P2X7 hypo) P2X7 expression show that fusion only occurs between P2X7 hyper/P2X7 hyper and not between P2X7 hyper/P2X7 hypo or P2X7 hypo/P2X7 hypo. During MGCs formation we detected activation of caspase 3, an enzyme that is powerfully stimulated by P2X7. Finally, we observed that during MGCs formation, the P2X7 receptor is preferentially localized at sites of cell-to-cell contact. These findings support the hypothesis originally put forward by our group that the P2X7 receptor participates in multinucleated giant cell formation.

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