Role of neuron-derived ATP in paclitaxel-induced HMGB1 release from macrophages and peripheral neuropathy
Risa Domoto, Fumiko Sekiguchi, Riki Kamaguchi, Maiko Iemura, Hiroki Yamanishi, Maho Tsubota, Dengli Wang, Masahiro Nishibori, Atsufumi Kawabata
Abstract
We examined the role of ATP and high mobility group box 1 (HMGB1) in paclitaxel-induced peripheral neuropathy (PIPN). PIPN in mice was prevented by HMGB1 neutralization, macrophage depletion, and P2X7 or P2X4 blockade. Paclitaxel and ATP synergistically released HMGB1 from macrophage-like RAW264.7 cells, but not neuron-like NG108-15 cells. The paclitaxel-induced HMGB1 release from RAW264.7 cells was accelerated by co-culture with NG108-15 cells in a manner dependent on P2X7 or P2X4. Paclitaxel released ATP from NG108-15 cells, but not RAW264.7 cells. Thus, PIPN is considered to involve acceleration of HMGB1 release from macrophages through P2X7 and P2X4 activation by neuron-derived ATP.