Mechanically stimulated ATP release from mammalian cells: systematic review and meta-analysis

Body tissues are exposed to a complex mechanical environment, which is perceived by cells and converted to biochemical signals such as ATP release. We performed a meta-analysis of 278 systematically identified studies that investigated mechanically stimulated ATP release (MSAR) to quantify the amounts, kinetics and mechanisms of ATP release under normal and pathological conditions. Mechanically stimulated mammalian cells were shown to release 38.6 [95% confidence interval (CI): 18.2-81.8] amol ATP/cell on average with a characteristic time constant of 32 s (95% CI: 16-66). Analysis of ATP release mechanisms revealed the existence of conserved and tissue-specific release routes. We assessed ATP release in pathophysiological states, and found that ATP release was elevated in inflammation and injury, and attenuated in hereditary (such as cystic fibrosis) and metabolic (such as type II diabetes) conditions. Our study links cell-specific ATP release mechanisms to pathophysiological changes in ATP release and allows ATP release-targeting interventions to be mapped to site-specific effects. This work demonstrates that quantitative synthesis of basic research can generate non-trivial hypotheses and inform evidence-driven translational studies.