| First Author | Lemaire I | Year | 2011 |
| Journal | J Immunol | Volume | 187 |
| Issue | 7 | Pages | 3878-87 |
| PubMed ID | 21865551 | Mgi Jnum | J:179343 |
| Mgi Id | MGI:5301802 | Doi | 10.4049/jimmunol.1002780 |
| Citation | Lemaire I, et al. (2011) The P2X7 receptor and Pannexin-1 are both required for the promotion of multinucleated macrophages by the inflammatory cytokine GM-CSF. J Immunol 187(7):3878-87 |
| abstractText | The P2X(7) receptor (P2X(7)R), an ATP-gated ion channel, has been implicated in the process of cell-to-cell fusion into multinucleated macrophages (MA), but its contribution to MA fusion driven by physiological/pathological stimuli is not clearly established. Based on several lines of evidence, we demonstrate that P2X(7)R is critical for the induction of multinucleated MA by the inflammatory cytokine GM-CSF: 1) pharmacological inhibition of P2X(7)R with oxidized ATP (oATP), KN-62, and the selective antagonist A740003 abrogated GM-CSF action on rat alveolar MA and murine peritoneal MA; 2) a murine J774 P2X(7) low MA clone, selected for defective P2X(7)R function, was unresponsive; 3) MA from mice lacking P2X(7)R failed to respond to GM-CSF, in contrast to wild-type. GM-CSF also stimulated ATP-induced membrane permeabilization in J774 P2X(7) high MA and rat alveolar MA, an effect absent in the P2X(7) low MA clone and inhibited by the P2X(7) blockers oATP and KN-62. Notably, the stimulatory effects of GM-CSF on pore formation and MA fusion were both inhibited by blocking functional Pannexin-1 (Panx-1), and GM-CSF failed to stimulate MA fusion in cells from Panx-1 knockout mice. We provide further evidence that extracellular ATP release from peritoneal MA is dependent on P2X(7) but not on Panx-1 expression and that its metabolism to adenosine mediates P2X(7)-dependent MA fusion. These data demonstrate that both P2X(7) and Panx-1 are required for GM-CSF promotion of MA fusion but likely act independently through different signaling pathway(s). |
