Neutrophil sling: A new cell‐autonomous adhesive structure enabling rolling at high shear

Abstract

Cell flattening and long tethers are known to facilitate neutrophil rolling at shear stresses of 6 dyn/cm2 or higher. When DiI‐stained mouse neutrophils were allowed to roll on P‐selectin in a microfluidic device at a shear stress of 6–10 dyn/cm2 and footprints recorded using quantitative dynamic footprinting (qDF), we found that long tethers did not retract, but instead appeared as ‘slings’ at the front of rolling neutrophils. Slings were confirmed in an acute model of inflammation in vivo using intravital microscopy of mouse cremaster. P‐selectin‐glycoprotein‐ligand (PSGL)‐1 was presented as discrete patches while integrin LFA‐1 was expressed over the entire length on slings. As neutrophils rolled forward, slings wrapped around the rolling neutrophils and underwent a step‐wise peeling from the P‐selectin substrate enabled by the tandem failure of PSGL‐1 patches. Failure of PSGL‐1 patches was concomitant with spurts in rolling velocity. This study reveals a previously undiscovered cell‐autonomous adhesive structure, “sling”, which enables neutrophils to roll at high shear stress during inflammation. This study was supported by the American Heart Association‐11SDG7340005 (P.S.) and NIH EB02185 (K.L.).