Pivotal role of ATP in macrophages fast tracking wound repair and regeneration

Abstract Chronic wounds occurring during aging or diabetes pose a significant burden to patients. The classical four‐phase wound healing process has a 3–6 day lag before granulation starts to appear and it requires an intermediate step of activation of resident fibroblasts during the remodeling phase for production of collagen. This brief communication discusses published articles that demonstrate how the entire wound healing process can be fast tracked by intracellular ATP delivery, which triggers a novel pathway where alternatively activated macrophages play absolutely critical and central roles. This novel pathway involves an increase in proinflammatory cytokines (TNF, IL‐1β, IL‐6) and a chemokine (MCP‐1) release. This is followed by activation of purinergic receptor (a family of plasma membrane receptors found in almost all mammalian cells), production of platelets and platelet microparticles, and activation of ATP‐dependent chromatin remodeling enzymes. The end result is a massive influx and in situ proliferation of macrophages, increases in vascular endothelial growth factors that promote neovascularization, and most prominently, the direct production of collagen.