CD39 and neutrophils
CD39 is widely expressed in neutrophils and plays a key role in regulating neutrophil activity by controlling the extracellular purine energy gradient [56]. In addition, neutrophils express CD73 [57] and all four ADO receptors[58]. Neutrophils directly secrete ADO and inhibit its degradation. Furthermore, they release ATP following activation, which is subsequently hydrolyzed by CD39 and CD73 into ADO[59]. The inadequate activity of the CD39/CD73 axis is related to the amplification and uncontrolled activation of neutrophils [60], enhancement of their chemotactic function [61], and increased neutrophil adhesion to the vascular endothelium [60, 62].
Studies have shown that CD39 plays an important role in regulating neutrophil chemotaxis by facilitating the hydrolysis of eATP. Shah et al. demonstrated that eATP had a regulatory effect on the late stage of neutrophil recruitment [63]. Once neutrophils reach the ATP-rich region, blocking CD39 may promote the stop signal of neutrophil chemotaxis [64]. Chen et al. showed that hydrolysis of ATP by CD39 promoted neutrophil chemotaxis by activating the A3R [5]. Both A3R- and CD39-deficient mice showed impaired recruitment of neutrophils to inflammatory sites [61, 65]. Paradoxically, lipopolysaccharides (LPS)-induced accumulation of neutrophil into the lungs was enhanced in CD39-/- mice, which may be due to the loss of normal endothelial barrier and increased capillary leakage in CD39-/- mice [66].