Requirement of Myeloperoxidase for Neutrophil Spatial Sensing

Unlike bacteria using a temporal gradient-sensing mechanism, eukaryotic cells sense chemoattractant gradients spatially, that is, they can detect an external gradient as low as 1~2% across a cell diameter. However, the molecular level at which eukaryotic cells achieves spatial sensing remains unknown. Here we report that blood neutrophils migrated faster but completely lost spatially sensing to bacterial formyl peptide gradients when myeloperioxidase (MPO) was knocked out or its activity was inhibited. MPO promoted formyl peptides dissociation from their receptors and refreshed receptors’ capacity to sense external gradients. Therefore, neutrophil directional sensing occurs at the receptor level, prompt dissociation of ligands from their receptors ensures neutrophils migrating precisely toward spatial cues.