'Slings' enable neutrophil rolling at high shear

Most leukocytes can roll along the walls of venules at lowshear stress (1 dyn cm(-2)), but neutrophils have the ability to roll at tenfold higher shear stress in microvessels in vivo(1,2). The mechanisms involved in this shear-resistant rolling are known to involve cell flattening(3) and pulling of long membrane tethers at the rear(4-6). Here we show that these long tethers do not retract as postulated(6,7), but instead persist and appear as 'slings' at the front of rolling cells. We demonstrate slings in a model of acute inflammationin vivo and on P-selectin in vitro, where P-selectin-glycoprotein-ligand-1 (PSGL-1) is found in discrete sticky patches whereas 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 previously(4-6,8). Each sling effectively lays out a cell-autonomous adhesive substrate in front of neutrophils rolling at high shear stress during inflammation.