TY - JOUR TI - Blood flow guides sequential support of neutrophil arrest and diapedesis by PILR-β1 and PILR-α AU - Li, Yu-Tung AU - Goswami, Debashree AU - Follmer, Melissa AU - Artz, Annette AU - Pacheco-Blanco, Mariana AU - Vestweber, Dietmar A2 - Fässler, Reinhard A2 - Taniguchi, Tadatsugu A2 - Sánchez Madrid, Francisco VL - 8 PY - 2019 DA - 2019/08/06 SP - e47642 C1 - eLife 2019;8:e47642 DO - 10.7554/eLife.47642 UR - https://doi.org/10.7554/eLife.47642 AB - Arrest of rapidly flowing neutrophils in venules relies on capturing through selectins and chemokine-induced integrin activation. Despite a long-established concept, we show here that gene inactivation of activating paired immunoglobulin-like receptor (PILR)-β1 nearly halved the efficiency of neutrophil arrest in venules of the mouse cremaster muscle. We found that this receptor binds to CD99, an interaction which relies on flow-induced shear forces and boosts chemokine-induced β2-integrin-activation, leading to neutrophil attachment to endothelium. Upon arrest, binding of PILR-β1 to CD99 ceases, shifting the signaling balance towards inhibitory PILR-α. This enables integrin deactivation and supports cell migration. Thus, flow-driven shear forces guide sequential signaling of first activating PILR-β1 followed by inhibitory PILR-α to prompt neutrophil arrest and then transmigration. This doubles the efficiency of selectin-chemokine driven neutrophil arrest by PILR-β1 and then supports transition to migration by PILR-α. KW - leukocyte extravasation KW - neutrophils KW - inflammation KW - endothelium KW - integrins JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -