Neutrophils scan for activated platelets to initiate inflammation

TLDR

Immune and inflammatory responses require leukocytes to migrate within and through the vasculature, a process that is facilitated by their capacity to switch to a polarized morphology with an asymmetric distribution of receptors. The selectin ligand PSGL‑1 transduces signals from neutrophil–platelet interactions, causing receptor redistribution that drives neutrophil migration. Neutrophil polarization in activated venules creates a protruding domain that engages activated platelets, and loss of polarization or PSGL‑1 signaling leads to aberrant crawling while blocking this domain protects mice from thromboinflammatory injury; these results demonstrate that neutrophils scan for activated platelets and that their bipolarity integrates endothelial and circulating signals to initiate inflammation.

Abstract

Immune and inflammatory responses require leukocytes to migrate within and through the vasculature, a process that is facilitated by their capacity to switch to a polarized morphology with an asymmetric distribution of receptors. We report that neutrophil polarization within activated venules served to organize a protruding domain that engaged activated platelets present in the bloodstream. The selectin ligand PSGL-1 transduced signals emanating from these interactions, resulting in the redistribution of receptors that drive neutrophil migration. Consequently, neutrophils unable to polarize or to transduce signals through PSGL-1 displayed aberrant crawling, and blockade of this domain protected mice against thromboinflammatory injury. These results reveal that recruited neutrophils scan for activated platelets, and they suggest that the neutrophils' bipolarity allows the integration of signals present at both the endothelium and the circulation before inflammation proceeds.