The neutrophil as firefighter

Severe bacterial infection or trauma frequently leads to a systemic inflammatory response, a self-reinforcing activation of neutrophils and vascular endothelial cells that can be deadly. On page 641, Cepinskas et al. describe a neutrophil-mediated signaling mechanism that inhibits inflammation. The findings demonstrate a novel function for neutrophils and a previously unknown form of immunological tolerance, and they identify a promising target for new anti-inflammatory drugs.

In systemic inflammation, circulating cytokines cause the transcription factor NFκB to translocate from the cytoplasm to the nucleus of vascular endothelial cells, where it induces the transcription of pro-inflammatory genes. Using a cell culture model of inflammation, the authors found that the migration of neutrophils across a monolayer of cytokine-activated endothelial cells causes NFκB levels in the endothelial cell nuclei to drop. Cross-linking the adhesion...