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].