Slings’ enable neutrophil rolling at high shear. Nature 488: 399–403

Most leukocytes can roll along the walls of venules at low shear stress (1 dyn/cm2), but neutrophils have the ability to roll at 10-fold higher shear stress in microvessels in vivo1,2. The mechanisms involved in this shear-resistant rolling are known to involve cell flattening3 and pulling of long membrane tethers at the rear4–6. Here, we show that these long tethers do not retract as postulated6,7, but instead persist and appear as ‘slings ’ at the front of rolling cells. We demonstrate slings in a model of acute inflammation in vivo and on P-selectin in vitro, where P-selectin-glycoprotein-ligand-1 (PSGL-1) is presented as discrete sticky patches while LFA-1 is expressed over the entire length on slings. As neutrophils roll forward, slings wrap around the rolling cells and undergo a step-wise peeling from the P-selectin substrate enabled by the failure of PSGL-1 patches under hydrodynamic forces. The ‘step-wise peeling of slings ’ is distinct from the ‘pulling of tethers ’ reported previously4–6,8. Each sling effectively lays out a cell-autonomous adhesive substrate in front of neutrophils rolling at high shear stress during inflammation. Neutrophil rolling at high shear stress is poorly understood2. Some neutrophil adhesion molecules including PSGL-1 are concentrated around the tips of microvilli, where the