Purinergic signaling integrates local excitation and global inhibition signals that regulate neutrophil chemotaxis

Abstract

Neutrophil chemotaxis requires local excitatory signals at the front and inhibitory signals at the back of cells. The mechanisms that link these signals are unknown. We previously showed that chemoattractants induce ATP release and excitatory purinergic feedback mechanisms at the front. Here we show that pannexin‐1 (panx1) is responsible for ATP release and that chemotaxis requires translocation of panx1 to the front and A2a adenosine receptors (A2aR) to the back. Panx1 provides both, ATP and adenosine, to elicit the excitatory and inhibitory signals at the front and back of cells. Inhibition of panx1 with carbenoxolone (CBX) completely abolished chemotaxis, while inhibition of A2aR with the antagonist CSC reduced migration speed (Fig. 1). Our findings demonstrate that panx1 is the molecular link that integrates the excitatory and inhibitory purinergic feedback mechanisms that regulate chemotaxis at the front and back of cells.This work was funded by grants from the National Institutes of Health and the Congressionally Directed Medical Research Program.