Role of neuron-derived ATP in paclitaxel-induced HMGB1 release from macrophages and peripheral neuropathy

• Published in: Journal of pharmacological sciences 2022-01, Vol.148 (1), p.156-161
• Main Authors: Domoto, Risa, Sekiguchi, Fumiko, Kamaguchi, Riki, Iemura, Maiko, Yamanishi, Hiroki, Tsubota, Maho, Wang, Dengli, Nishibori, Masahiro, Kawabata, Atsufumi
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate - physiology; Animals; ATP; Chemotherapy-induced peripheral neuropathy (CIPN); High mobility group box 1 (HMGB1); HMGB1 Protein - metabolism; Macrophages - metabolism; Male; Mice; Mice, Inbred Strains; Neuroimmune crosstalk; Neurons - metabolism; Paclitaxel; Paclitaxel - adverse effects; Peripheral Nervous System Diseases - chemically induced; Peripheral Nervous System Diseases - immunology; Peripheral Nervous System Diseases - metabolism; Peripheral Nervous System Diseases - prevention & control; RAW 264.7 Cells; Receptor Cross-Talk - immunology; Receptors, Purinergic P2X4 - metabolism; Receptors, Purinergic P2X7 - metabolism
• ISSN: 1347-8613; 1347-8648
• DOI: 10.1016/j.jphs.2021.11.003

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.