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

J Pharmacol Sci. 2022 Jan;148(1):156-161. doi: 10.1016/j.jphs.2021.11.003. Epub 2021 Nov 12.

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.

Keywords: ATP; Chemotherapy-induced peripheral neuropathy (CIPN); High mobility group box 1 (HMGB1); Neuroimmune crosstalk; Paclitaxel.

MeSH terms

  • Adenosine Triphosphate / physiology*
  • Animals
  • HMGB1 Protein / metabolism*
  • Macrophages / metabolism*
  • Male
  • Mice
  • Mice, Inbred Strains
  • Neurons / metabolism*
  • 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

Substances

  • HMGB1 Protein
  • HMGB1 protein, mouse
  • P2rx7 protein, mouse
  • Receptors, Purinergic P2X4
  • Receptors, Purinergic P2X7
  • Adenosine Triphosphate
  • Paclitaxel