Role of purinergic signaling during neutrophil-endothelial transmigration. During neutrophil-endothelial transmigration, purinergic signaling events play a critical role in coordinating neutrophil movements toward a chemotactic gradient (purinergic chemotaxis), opening of the endothelial barrier, and subsequent resealing of the endothelial monolayer. ATP released from the leading edge of a neutrophil (yellow circle), activation of PMN-dependent ATP receptors (particularly the P2Y2R), conversion of ATP to adenosine (red circle) by the ectonucleotidase CD39 and CD73, and adenosine signaling through PMN-dependent A3 adenosine receptors are involved in promoting PMN movements toward a chemotactic gradient (“inflammation”). Similarly, purinergic signaling is involved in opening up the endothelial barrier function. For example, endothelial P2Y6Rs have been implicated in opening up the endothelial barrier function during inflammatory conditions. Interestingly, a subsequent set of purinergic signaling events is critical to resealing of the endothelial barrier function and in attenuating PMN-elicited inflammation, thereby initiating the “resolution of inflammation.” As such, activation of ADORA2B adenosine receptors (A2B) on vascular endothelial cells functions to increase the vascular barrier function, whereas ADORA2B and ADORA2A signaling (A2A, A2B) on PMN dampens neutrophil-elicited inflammation.