| First Author | Li YT | Year | 2019 |
| Journal | Elife | Volume | 8 |
| PubMed ID | 31385804 | Mgi Jnum | J:286045 |
| Mgi Id | MGI:6400119 | Doi | 10.7554/eLife.47642 |
| Citation | Li YT, et al. (2019) Blood flow guides sequential support of neutrophil arrest and diapedesis by PILR-beta1 and PILR-alpha. Elife 8:e47642 |
| abstractText | 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)-beta1 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 beta2-integrin-activation, leading to neutrophil attachment to endothelium. Upon arrest, binding of PILR-beta1 to CD99 ceases, shifting the signaling balance towards inhibitory PILR-alpha. This enables integrin deactivation and supports cell migration. Thus, flow-driven shear forces guide sequential signaling of first activating PILR-beta1 followed by inhibitory PILR-alpha to prompt neutrophil arrest and then transmigration. This doubles the efficiency of selectin-chemokine driven neutrophil arrest by PILR-beta1 and then supports transition to migration by PILR-alpha. |
