P2X(7) receptor and polykarion formation

Cell fusion is a central phenomenon during the immune response that leads t o formation of large elements called multinucleated giant cells (MGCs) of c ommon 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 P2X(7) receptor. Here in, we show that blockade of this receptor by a specific monoclonal antibod y prevents fusion in vitro. In contrast, cell fusion is stimulated by addit ion of enzymes that destroy extracellular ATP (i.e., apyrase or hexokinase) . Experiments performed with phagocytes selected for high (P2X(7) hyper) or low (P2X(7) hypo) P2X(7) expression show that fusion only occurs between P 2X(7) hyper/P2X(7) hyper and not between P2X(7) hyper/P2X(7) hypo or P2X(7) hypo/P2X(7) hypo. During MGCs formation we detected activation of caspase 3, an enzyme that is powerfully stimulated by P2X(7). Finally, we observed that during MGCs formation, the P2X(7) receptor is preferentially localized at sites of cell-to-cell contact. These findings support the hypothesis or iginally put forward by our group that the P2X(7) receptor participates in multinucleated giant cell formation.