Neutrophils cast slings against the flow

Abstract

During inflammation neutrophils roll slowly on microvessel walls, prior to their extravasation. Cell flattening and long rear membrane tethers maintain slow neutrophil rolling at high shear stress. Here, Sundd et al. report that 'slings' forming at the front of rolling neutrophils can also act as potent breaks during rolling. In vitro and in vivo imaging showed that detached tethers swing to the front of rolling neutrophils to form long slings that contain 'sticky patches' of the P-selectin ligand PSGL1. As neutrophils roll over the sling and transfer load between consecutive PSGL1 patches, the interaction between LFA1 on slings and ICAM2 on the neutrophil surface ensures tight neutrophil wrapping by slings, thereby retaining them close to the microvessel wall. Interestingly, measurements of the forces applied by tethers and slings on rolling neutrophils indicate that these structures could be sufficient for slow neutrophil rolling at high shear stress.