Extracellular ATP (eATP) inhibits the progression of endometriosis and enhances the immune function of macrophages.

BACKGROUND

Extracellular adenosine triphosphate (eATP) is an important inflammatory mediator that can boost the antitumour immune response, but its role in endometriosis remains unknown. We hypothesized that eATP could inhibit endometriosis cell function both directly and indirectly through macrophages.

METHODS

Peritoneal and cyst fluid from endometriosis patients and non-endometriosis controls was collected to measure eATP levels. The addition of eATP was performed to explore its effects on endometriotic cell and macrophage functions, including cell proliferation, apoptosis, pyroptosis, mitochondrial membrane potential, phagocytosis, and the production of inflammatory cytokines and reactive oxygen species. A coculture of endometriotic epithelial cells and U937 macrophages was established, followed by P2X7 antagonist and eATP treatment. Endometriosis model eATP-treated rats were used to evaluate in situ cell death and macrophage marker expression.

RESULTS

The pelvic microenvironment of endometriosis patients shows high eATP levels, which could induce endometriotic epithelial cell apoptosis and pyroptosis and significantly inhibit cell growth via the MAPK/JNK/Akt pathway. eATP treatment ameliorated endometriosis-related macrophage dysfunction and promoted macrophage recruitment. eATP treatment in the presence of macrophages exerted a stronger cytotoxic effect on endometriotic epithelial cells by regulating P2X7. eATP treatment effectively induced cell death in an endometriosis rat model and prominently increased the macrophage number without affecting the eutopic endometrium.

CONCLUSION

eATP induces endometriotic epithelial cell death and enhances the immune function of macrophages to inhibit the progression of endometriosis, while eutopic endometrium is not affected. eATP treatment may serve as a nonhormonal therapeutic strategy for endometriosis.